Section 49-4 Review Drugs and the Nervous System Answers

Chemical substance that enables neurotransmission

For an introduction to concepts and terminology used in this article, run into Chemical synapse.

Structure of a typical chemical synapse
Postsynaptic density Voltage- gated Ca++ channel Synaptic vesicle Neurotransmitter transporter Receptor Neurotransmitter Axon terminal Synaptic cleft Dendrite

A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The jail cell receiving the signal, any main trunk part or target cell, may be another neuron, only could also be a gland or muscle cell.^[1]

Neurotransmitters are released from synaptic vesicles into the synaptic cleft where they are able to collaborate with neurotransmitter receptors on the target cell. The neurotransmitter's event on the target prison cell is determined by the receptor information technology binds. Many neurotransmitters are synthesized from simple and plentiful precursors such every bit amino acids, which are readily available and frequently crave a small number of biosynthetic steps for conversion.

Neurotransmitters are essential to the role of complex neural systems. The verbal number of unique neurotransmitters in humans is unknown, but more than 100 have been identified.^[2] Common neurotransmitters include glutamate, GABA, acetylcholine, glycine and norepinephrine.

Mechanism and bike [edit]

Synthesis [edit]

Neurotransmitters are more often than not synthesized in neurons and are made up of, or derived from, forerunner molecules that are constitute abundantly in the cell. Classes of neurotransmitters include amino acids, monoamines, and peptides. Monoamines are synthesized by altering a unmarried amino acid. For case, the precursor of serotonin is the amino acid tryptophan. Peptide transmitters, or neuropeptides, are protein transmitters that often are released together with other transmitters to have a modulatory effect.^[iii] Purine neurotransmitters, similar ATP, are derived from nucleic acids. Other neurotransmitters are made up of metabolic products similar nitric oxide and carbon monoxide.

	Examples
Amino Acrid	glycine, glutamate
Monoamines	serotonin, epinephrine, dopamine
Peptides	substance P, opioids
Purines	ATP, GTP
Other	nitric oxide, carbon monoxide

Synaptic vesicles containing neurotransmitters

Storage [edit]

Neurotransmitters are generally stored in synaptic vesicles, clustered shut to the jail cell membrane at the axon terminal of the presynaptic neuron. Still, some neurotransmitters, similar the metabolic gases carbon monoxide and nitric oxide, are synthesized and released immediately post-obit an action potential without always being stored in vesicles.^[4]

Release [edit]

Generally, a neurotransmitter is released at the presynaptic terminal in response to an electric bespeak called an activity potential in the presynaptic neuron. However, low level 'baseline' release also occurs without electrical stimulation. Neurotransmitters are released into and diffuse beyond the synaptic cleft, where they demark to specific receptors on the membrane of the postsynaptic neuron.^[five]

Receptor interaction [edit]

Subsequently beingness released into the synaptic fissure, neurotransmitters diffuse across the synapse where they are able to interact with receptors on the target cell. The event of the neurotransmitter is dependent on the identity of the target cell's receptors present at the synapse. Depending on the receptor, binding of neurotransmitters may crusade excitation, inhibition, or modulation of the postsynaptic neuron. See below for more information.

Elimination [edit]

Acetylcholine is cleaved in the synaptic scissure into acerb acid and choline

In order to avoid continuous activation of receptors on the post-synaptic or target cell, neurotransmitters must be removed from the synaptic cleft.^{[half dozen]} Neurotransmitters are removed through one of 3 mechanisms:

1. Diffusion – neurotransmitters drift out of the synaptic cleft, where they are absorbed by glial cells. These glial cells, usually astrocytes, absorb the excess neurotransmitters. In the glial jail cell, neurotransmitters are cleaved down by enzymes or pumped dorsum into
2. Enzyme degradation – proteins chosen enzymes break the neurotransmitters down.
3. Reuptake – neurotransmitters are reabsorbed into the pre-synaptic neuron. Transporters, or membrane ship proteins, pump neurotransmitters from the synaptic cleft back into axon terminals (the presynaptic neuron) where they are stored for reuse.

For example, acetylcholine is eliminated past having its acetyl group broken by the enzyme acetylcholinesterase; the remaining choline is and so taken in and recycled by the pre-synaptic neuron to synthesize more acetylcholine.^[7] Other neurotransmitters are able to diffuse away from their targeted synaptic junctions and are eliminated from the body via the kidneys, or destroyed in the liver. Each neurotransmitter has very specific degradation pathways at regulatory points, which may be targeted by the body'south regulatory organisation or medication. Cocaine blocks a dopamine transporter responsible for the reuptake of dopamine. Without the transporter, dopamine diffuses much more than slowly from the synaptic cleft and continues to actuate the dopamine receptors on the target cell.^[8]

Discovery [edit]

Until the early 20th century, scientists causeless that the majority of synaptic communication in the brain was electrical. However, through histological examinations by Ramón y Cajal, a 20 to xl nm gap between neurons, known today equally the synaptic cleft, was discovered. The presence of such a gap suggested communication via chemical messengers traversing the synaptic crevice, and in 1921 German pharmacologist Otto Loewi confirmed that neurons can communicate by releasing chemicals. Through a series of experiments involving the vagus fretfulness of frogs, Loewi was able to manually slow the heart charge per unit of frogs by controlling the corporeality of saline solution present effectually the vagus nervus. Upon completion of this experiment, Loewi asserted that sympathetic regulation of cardiac function can be mediated through changes in chemic concentrations. Furthermore, Otto Loewi is credited with discovering acetylcholine (ACh) – the beginning known neurotransmitter.^[ix]

Identification [edit]

There are four master criteria for identifying neurotransmitters:

1. The chemical must be synthesized in the neuron or otherwise be present in it.
2. When the neuron is active, the chemical must be released and produce a response in some targets.
3. The same response must be obtained when the chemical is experimentally placed on the target.
4. A machinery must exist for removing the chemical from its site of activation after its work is washed.

Nonetheless, given advances in pharmacology, genetics, and chemical neuroanatomy, the term "neurotransmitter" tin be practical to chemicals that:

• Bear letters between neurons via influence on the postsynaptic membrane.
• Have little or no upshot on membrane voltage, just take a common conveying function such every bit changing the construction of the synapse.
• Communicate by sending reverse-direction messages that affect the release or reuptake of transmitters.

The anatomical localization of neurotransmitters is typically determined using immunocytochemical techniques, which place the location of either the transmitter substances themselves or of the enzymes that are involved in their synthesis. Immunocytochemical techniques take also revealed that many transmitters, peculiarly the neuropeptides, are co-localized, that is, a neuron may release more than one transmitter from its synaptic final.^[x] Various techniques and experiments such as staining, stimulating, and collecting tin be used to identify neurotransmitters throughout the primal nervous organization.^[11]

Deportment [edit]

Neurons form elaborate networks through which nerve impulses – activity potentials – travel. Each neuron has every bit many every bit xv,000 connections with neighboring neurons.

Neurons do not touch each other (except in the case of an electrical synapse through a gap junction); instead, neurons interact at contact points called synapses: a junction within ii nerve cells, consisting of a miniature gap within which impulses are carried by a neurotransmitter. A neuron transports its information past way of a nerve impulse chosen an action potential. When an activeness potential arrives at the synapse's presynaptic terminal push, it may stimulate the release of neurotransmitters. These neurotransmitters are released into the synaptic cleft to demark onto the receptors of the postsynaptic membrane and influence some other cell, either in an inhibitory or excitatory style. The next neuron may be connected to many more neurons, and if the total of excitatory influences minus inhibitory influences is great enough, it will likewise "fire". That is to say, it will create a new activeness potential at its axon hillock, releasing neurotransmitters and passing on the information to yet another neighboring neuron.

Modulation [edit]

A neurotransmitter may have an excitatory, inhibitory or modulatory effect on the target cell. The effect is determined past the receptors the neurotransmitter interacts with at the postal service-synaptic membrane. Neurotransmitter influences trans-membrane ion menstruation either to increase (excitatory) or to subtract (inhibitory) the probability that the cell with which it comes in contact will produce an activeness potential. Synapses containing receptors with excitatory effects are called Blazon I synapses, while Type 2 synapses contain receptors with inhibitory furnishings.^[12] Thus, despite the wide variety of synapses, they all convey messages of only these two types. The two types are different advent and are primarily located on unlike parts of the neurons under its influence.^[13] Receptors with modulatory effects are spread throughout all synaptic membranes and binding of neurotransmitters sets in motion signaling cascades that assistance the cell regulate its part.^[14] Binding of neurotransmitters to receptors with modulatory effects can have many results. For example it may result in an increase or decrease in sensitivity to future stimulus by recruiting more or less receptors to the synaptic membrane.

Type I (excitatory) synapses are typically located on the shafts or the spines of dendrites, whereas type II (inhibitory) synapses are typically located on a cell body. In improver, Type I synapses have round synaptic vesicles, whereas the vesicles of type II synapses are flattened. The material on the presynaptic and post-synaptic membranes is denser in a Type I synapse than it is in a type II, and the type I synaptic cleft is wider. Finally, the active zone on a Type I synapse is larger than that on a Blazon II synapse.

The unlike locations of type I and blazon II synapses split up a neuron into two zones: an excitatory dendritic tree and an inhibitory prison cell torso. From an inhibitory perspective, excitation comes in over the dendrites and spreads to the axon hillock to trigger an action potential. If the message is to be stopped, it is best stopped by applying inhibition on the cell body, close to the axon hillock where the activity potential originates. Another fashion to anticipate excitatory–inhibitory interaction is to moving-picture show excitation overcoming inhibition. If the cell trunk is ordinarily in an inhibited land, the just way to generate an action potential at the axon hillock is to reduce the jail cell body's inhibition. In this "open the gates" strategy, the excitatory bulletin is like a racehorse ready to run downward the rails, but offset, the inhibitory starting gate must be removed.^[15]

Neurotransmitter deportment [edit]

As explained above, the only direct activity of a neurotransmitter is to actuate a receptor. Therefore, the effects of a neurotransmitter system depend on the connections of the neurons that use the transmitter, and the chemical properties of the receptors.

• Glutamate is used at the great majority of fast excitatory synapses in the brain and spinal cord. Information technology is also used at almost synapses that are "modifiable", i.e. capable of increasing or decreasing in strength. Modifiable synapses are thought to be the main retentivity-storage elements in the brain. Excessive glutamate release can overstimulate the brain and lead to excitotoxicity causing cell decease resulting in seizures or strokes.^[16] Excitotoxicity has been implicated in certain chronic diseases including ischemic stroke, epilepsy, amyotrophic lateral sclerosis, Alzheimer's disease, Huntington affliction, and Parkinson's affliction.^[17]

• GABA is used at the great majority of fast inhibitory synapses in virtually every part of the brain. Many allaying/tranquilizing drugs human activity by enhancing the effects of GABA.^[18] Correspondingly, glycine is the inhibitory transmitter in the spinal string.

• Acetylcholine was the first neurotransmitter discovered in the peripheral and central nervous systems. Information technology activates skeletal muscles in the somatic nervous arrangement and may either excite or inhibit internal organs in the autonomic arrangement.^[xi] It is distinguished as the transmitter at the neuromuscular junction connecting motor nerves to muscles. The paralytic arrow-poisonous substance curare acts by blocking manual at these synapses. Acetylcholine besides operates in many regions of the brain, but using different types of receptors, including nicotinic and muscarinic receptors.^[19]

• Dopamine has a number of important functions in the encephalon; this includes regulation of motor behavior, pleasures related to motivation and too emotional arousal. It plays a critical role in the advantage organisation; Parkinson'south illness has been linked to low levels of dopamine and schizophrenia has been linked to loftier levels of dopamine.^[20]

• Serotonin is a monoamine neurotransmitter. Well-nigh is produced by and found in the intestine (approximately ninety%), and the remainder in central nervous system neurons. It functions to regulate appetite, sleep, memory and learning, temperature, mood, behaviour, muscle contraction, and function of the cardiovascular system and endocrine organisation. It is speculated to have a part in depression, as some depressed patients are seen to have lower concentrations of metabolites of serotonin in their cerebrospinal fluid and brain tissue.^[21]

• Norepinephrine which is synthesized in the central nervous system and sympathetic fretfulness, modulates the responses of the autonomic nervous arrangement, the slumber patterns, focus and alacrity. It is synthesized from tyrosine.

• Epinephrine which is also synthesized from tyrosine is released in the adrenal glands and the brainstem. It plays a role in sleep, with one's power to get and stay alert, and the fight-or-flight response.

Types [edit]

At that place are many different means to classify neurotransmitters. Dividing them into amino acids, peptides, and monoamines is sufficient for some classification purposes.^[22]

Major neurotransmitters:

• Amino acids: glutamate,^[23] aspartate, D-serine, gamma-Aminobutyric acid (GABA),^{[nb 1]} glycine
• Gasotransmitters: nitric oxide (NO), carbon monoxide (CO), hydrogen sulfide (H_iiS)
• Monoamines: dopamine (DA), norepinephrine (noradrenaline; NE, NA), epinephrine (adrenaline), histamine, serotonin (SER, 5-HT)
  • Catecholamines: dopamine, norepinephrine (noradrenaline), epinephrine (adrenaline)
• Trace amines: phenethylamine, N-methylphenethylamine, tyramine, iii-iodothyronamine, octopamine, tryptamine, etc.
• Peptides: oxytocin, somatostatin, substance P, cocaine and amphetamine regulated transcript, opioid peptides^[24]
• Purines: adenosine triphosphate (ATP), adenosine
• Others: acetylcholine (ACh), anandamide, etc.

In addition, over 100 neuroactive peptides accept been found, and new ones are discovered regularly.^{[25] [26]} Many of these are co-released along with a small-molecule transmitter. All the same, in some cases, a peptide is the main transmitter at a synapse. Beta-Endorphin is a relatively well-known example of a peptide neurotransmitter because it engages in highly specific interactions with opioid receptors in the central nervous system.

Single ions (such as synaptically released zinc) are also considered neurotransmitters past some,^[27] as well as some gaseous molecules such as nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H₂S).^[28] The gases are produced in the neural cytoplasm and are immediately diffused through the cell membrane into the extracellular fluid and into nearby cells to stimulate product of 2d messengers. Soluble gas neurotransmitters are difficult to study, as they act rapidly and are immediately broken downwards, existing for only a few seconds.

The most prevalent transmitter is glutamate, which is excitatory at well over 90% of the synapses in the human encephalon.^[23] The adjacent most prevalent is gamma-Aminobutyric Acid, or GABA, which is inhibitory at more than 90% of the synapses that do not use glutamate. Although other transmitters are used in fewer synapses, they may be very important functionally: the corking majority of psychoactive drugs exert their effects by altering the actions of some neurotransmitter systems, oft acting through transmitters other than glutamate or GABA. Addictive drugs such equally cocaine and amphetamines exert their furnishings primarily on the dopamine organization. The addictive opiate drugs exert their effects primarily equally functional analogs of opioid peptides, which, in turn, regulate dopamine levels.

List of neurotransmitters, peptides, and gaseous signaling molecules [edit]

Neurotransmitters

Category	Name	Abbreviation	Metabotropic	Ionotropic
Minor: Amino acids (Arg)	Arginine	Arg, R	α2-Adrenergic receptors, imidazoline receptors	NMDA receptors
Small-scale: Amino acids	Aspartate	Asp, D	–	NMDA receptors
Small: Amino acids	Glutamate	Glu, E	Metabotropic glutamate receptors	NMDA receptors, kainate receptors, AMPARs
Pocket-sized: Amino acids	Gamma-aminobutyric acid	GABA	GABAB receptors	GABAA receptors, GABAA-ρ receptors
Pocket-size: Amino acids	Glycine	Gly, One thousand	–	NMDA receptors, glycine receptors
Small: Amino acids	D-serine	Ser, Southward	–	NMDA receptors
Small: Acetylcholine	Acetylcholine	ACh	Muscarinic acetylcholine receptors	Nicotinic acetylcholine receptors
Small: Monoamine (Phe/Tyr)	Dopamine	DA	Dopamine receptors, trace amine-associated receptor one[29] [xxx]	–
Small-scale: Monoamine (Phe/Tyr)	Norepinephrine (noradrenaline)	NE, NAd	Adrenergic receptors	–
Small: Monoamine (Phe/Tyr)	Epinephrine (adrenaline)	Epi, Advert	Adrenergic receptors	–
Small: Monoamine (Trp)	Serotonin (five-hydroxytryptamine)	5-HT	Serotonin receptors (all except 5-HT3)	v-HT3
Small: Monoamine (His)	Histamine	H	Histamine receptors	–
Pocket-sized: Trace amine (Phe)	Phenethylamine	PEA	Homo trace amine-associated receptors: hTAAR1, hTAAR2	–
Small-scale: Trace amine (Phe)	Northward-methylphenethylamine	NMPEA	hTAAR1	–
Small-scale: Trace amine (Phe/Tyr)	Tyramine	TYR	hTAAR1, hTAAR2	–
Small: Trace amine (Phe/Tyr)	octopamine	Oct	hTAAR1	–
Small: Trace amine (Phe/Tyr)	Synephrine	Syn	hTAAR1	–
Small: Trace amine (Trp)	Tryptamine		hTAAR1, various serotonin receptors	–
Small: Trace amine (Trp)	N-methyltryptamine	NMT	hTAAR1, various serotonin receptors	–
Lipid	Anandamide	AEA	Cannabinoid receptors	–
Lipid	2-Arachidonoylglycerol	2-AG	Cannabinoid receptors	–
Lipid	ii-Arachidonyl glyceryl ether	2-AGE	Cannabinoid receptors	–
Lipid	Due north-Arachidonoyl dopamine	Goose egg	Cannabinoid receptors	TRPV1
Lipid	Virodhamine		Cannabinoid receptors	–
Small: Purine	Adenosine	Ado	Adenosine receptors	–
Small: Purine	Adenosine triphosphate	ATP	P2Y receptors	P2X receptors
Pocket-sized: Purine	Nicotinamide adenine dinucleotide	β-NAD	P2Y receptors	P2X receptors

Neuropeptides

Category	Proper noun	Abbreviation	Metabotropic	Ionotropic
Bombesin-like peptides	Bombesin		BBR1-2-3	–
Bombesin-like peptide	Gastrin releasing peptide	GRP	–	–
Bombesin-similar peptide	Neuromedin B	NMB	Neuromedin B receptor	–
Bradykinins	Bradykinin		B1, B2	–
Calcitonin/CGRP family	Calcitonin		Calcitonin receptor	–
Calcitonin/CGRP family unit	Calcitonin cistron-related peptide	CGRP	CALCRL	–
Corticotropin-releasing factors	Corticotropin-releasing hormone	CRH	CRHR1	–
Corticotropin-releasing factors	Urocortin		CRHR1	–
Galanins	Galanin		GALR1, GALR2, GALR3	–
Galanins	Galanin-like peptide		GALR1, GALR2, GALR3	–
Gastrins	Gastrin		Cholecystokinin B receptor	–
Gastrins	Cholecystokinin	CCK	Cholecystokinin receptors	–
Granins	Chromogranin A	ChgA	–	–
Melanocortins	Adrenocorticotropic hormone	ACTH	ACTH receptor	–
Melanocortins	Proopiomelanocortin	POMC	Melanocortin four receptor	–
Melanocortins	Melanocyte-stimulating hormones	MSH	Melanocortin receptors	–
Neurohypophyseals	Vasopressin	AVP	Vasopressin receptors	–
Neurohypophyseals	Oxytocin	OT	Oxytocin receptor	–
Neurohypophyseals	Neurophysin I		–	–
Neurohypophyseals	Neurophysin Ii		–	–
Neurohypophyseals	Copeptin		–	–
Neuromedins	Neuromedin U	NmU	NmUR1, NmUR2	–
Neuropeptide B/W	Neuropeptide B	NPB	NPBW1, NPBW2	–
Neuropeptide B/W	Neuropeptide South	NPS	Neuropeptide Due south receptors	–
Neuropeptide Y	Neuropeptide Y	NY	Neuropeptide Y receptors	–
Neuropeptide Y	Pancreatic polypeptide	PP	–	–
Neuropeptide Y	Peptide YY	PYY	–	–
Opioids	Enkephalins		δ-Opioid receptor	–
Opioids	Dynorphins		κ-Opioid receptor	–
Opioids	Neoendorphins		κ-Opioid receptor	–
Opioids	Endorphins		μ-Opioid receptors	–
Opioids	Endomorphins		μ-Opioid receptors	–
Opioids	Morphine		μ-Opioid receptors	–
Opioids	Nociceptin/orphanin FQ	Due north/OFQ	Nociceptin receptors	–
Orexins	Orexin A	OX-A	Orexin receptors	–
Orexins	Orexin B	OX-B	Orexin receptors	–
Parathyroid hormone family	Parathyroid hormone-related protein	PTHrP	–	–
RFamides	Kisspeptin	Osculation	GPR54	–
RFamides	Neuropeptide FF	NPFF	NPFF1, NPFF2	–
RFamides	Prolactin-releasing peptide	PrRP	PrRPR	–
RFamides	Pyroglutamylated RFamide peptide	QRFP	GPR103	–
Secretins	Secretin		Secretin receptor	–
Secretins	Motilin		Motilin receptor	–
Secretins	Glucagon		Glucagon receptor	–
Secretins	Glucagon-like peptide-1	GLP-one	Glucagon-like peptide one receptor	–
Secretins	Glucagon-like peptide-two	GLP-2	Glucagon-like peptide 2 receptor	–
Secretins	Vasoactive intestinal peptide	VIP	Vasoactive intestinal peptide receptors	–
Secretins	Growth hormone–releasing hormone	GHRH	Growth hormone–releasing hormone receptor	–
Secretins	Pituitary adenylate cyclase-activating peptide	PACAP	ADCYAP1R1	–
Somatostatins	Somatostatin		Somatostatin receptors	–
Tachykinins	Neurokinin A		–	–
Tachykinins	Neurokinin B		–	–
Tachykinins	Substance P		–	–
Tachykinins	Neuropeptide K		–	–
Other	Agouti-related peptide	AgRP	Melanocortin receptor –
Other	N-Acetylaspartylglutamate	NAAG	Metabotropic glutamate receptor iii (mGluR3)	–
Other	Cocaine- and amphetamine-regulated transcript	CART	Unknown One thousandi/One thousando-coupled receptor[31]	–
Other	Gonadotropin-releasing hormone	GnRH	GnRHR	–
Other	Thyrotropin-releasing hormone	TRH	TRHR	–
Other	Melanin-concentrating hormone	MCH	MCHR 1,2	–

Gasotransmitters

Category	Name	Abbreviation	Metabotropic	Ionotropic
Gaseous signaling molecule	Nitric oxide	NO	Soluble guanylyl cyclase	–
Gaseous signaling molecule	Carbon monoxide	CO	–	Heme jump to potassium channels
Gaseous signaling molecule	Hydrogen sulfide	H2S	–	–

Encephalon neurotransmitter systems [edit]

Neurons expressing certain types of neurotransmitters sometimes form singled-out systems, where activation of the system affects large volumes of the brain, chosen volume transmission. Major neurotransmitter systems include the noradrenaline (norepinephrine) system, the dopamine system, the serotonin system, and the cholinergic organization, amongst others. Trace amines accept a modulatory effect on neurotransmission in monoamine pathways (i.e., dopamine, norepinephrine, and serotonin pathways) throughout the encephalon via signaling through trace amine-associated receptor 1.^{[32] [33]} A brief comparison of these systems follows:

Neurotransmitter systems in the brain

System	Pathway origin and projections	Regulated cognitive processes and behaviors
Noradrenaline arrangement [34] [35] [36] [37] [38] [39]	Noradrenergic pathways: Locus coeruleus (LC) projections LC → Amygdala and Hippocampus LC → Brain stem and Spinal cord LC → Cerebellum LC → Cognitive cortex LC → Hypothalamus LC → Tectum LC → Thalamus LC → Ventral tegmental area Lateral tegmental field (LTF) projections LTF → Brain stem and Spinal cord LTF → Olfactory bulb	feet arousal (wakefulness) cyclic rhythm cognitive control and working retentiveness (co-regulated by dopamine) feeding and energy homeostasis medullary control of respiration negative emotional retentiveness nociception (perception of hurting) reward (minor function)
Dopamine system [36] [37] [38] [40] [41] [42]	Dopaminergic pathways: Ventral tegmental surface area (VTA) projections VTA → Amygdala VTA → Cingulate cortex VTA → Hippocampus VTA → Ventral striatum (Mesolimbic pathway) VTA → Olfactory bulb VTA → Prefrontal cortex (Mesocortical pathway) Nigrostriatal pathway Substantia nigra pars compacta → Dorsal striatum Tuberoinfundibular pathway Arcuate nucleus → Median eminence Hypothalamospinal project Hypothalamus → Spinal string Incertohypothalamic pathway Zona incerta → Hypothalamus	arousal (wakefulness) disfavor cognitive control and working retentivity (co-regulated past norepinephrine) emotion and mood motivation (motivational salience) motor part and control positive reinforcement reward (primary mediator) sexual arousal, orgasm, and refractory menstruum (via neuroendocrine regulation)
Histamine system [37] [38] [43]	Histaminergic pathways: Tuberomammillary nucleus (TMN) projections TMN → Cerebral cortex TMN → Hippocampus TMN → Neostriatum TMN → Nucleus accumbens TMN → Amygdala TMN → Hypothalamus	arousal (wakefulness) feeding and energy homeostasis learning memory
Serotonin system [34] [36] [37] [38] [44] [45] [46]	Serotonergic pathways: Caudal nuclei (CN): Raphe magnus, raphe pallidus, and raphe obscurus Caudal projections CN → Cerebral cortex CN → Thalamus CN → Caudate-putamen and nucleus accumbens CN → Substantia nigra and ventral tegmental area CN → Cerebellum CN → Spinal cord Rostral nuclei (RN): Nucleus linearis, dorsal raphe, medial raphe, and raphe pontis Rostral projections RN → Amygdala RN → Cingulate cortex RN → Hippocampus RN → Hypothalamus RN → Neocortex RN → Septum RN → Thalamus RN → Ventral tegmental area	arousal (wakefulness) trunk temperature regulation emotion and mood, potentially including aggression feeding and energy homeostasis reward (small-scale part) sensory perception
Acetylcholine system [34] [36] [37] [38] [47]	Cholinergic pathways: Forebrain cholinergic nuclei (FCN): Nucleus basalis of Meynert, medial septal nucleus, and diagonal band Forebrain nuclei projections FCN → Hippocampus FCN → Cerebral cortex FCN → Limbic cortex and sensory cortex Striatal tonically active cholinergic neurons (TAN) TAN → Medium spiny neuron Brainstem cholinergic nuclei (BCN): Pedunculopontine nucleus, laterodorsal tegmentum, medial habenula, and parabigeminal nucleus Brainstem nuclei projections BCN → Ventral tegmental area BCN → Thalamus	arousal (wakefulness) emotion and mood learning motor function motivation (motivational salience) short-term retentivity reward (pocket-sized function)
Adrenaline system [48] [49]	Adrenergic pathways: Rostral ventrolateral medulla (RVLM) projections RVLM → Spinal string RVLM → Brain stem RVLM → Hypothalamus	medullary control of respiration sympathetic nervous organisation feeding and energy homeostasis arousal stress

Drug effects [edit]

Understanding the furnishings of drugs on neurotransmitters comprises a significant portion of research initiatives in the field of neuroscience. Most neuroscientists involved in this field of research believe that such efforts may further advance our agreement of the circuits responsible for various neurological diseases and disorders, as well equally ways to effectively treat and someday possibly prevent or cure such illnesses.^{[fifty] [ medical citation needed ]}

Drugs can influence behavior by altering neurotransmitter action. For example, drugs tin can decrease the charge per unit of synthesis of neurotransmitters by affecting the synthetic enzyme(s) for that neurotransmitter. When neurotransmitter syntheses are blocked, the amount of neurotransmitters available for release becomes substantially lower, resulting in a decrease in neurotransmitter activeness. Some drugs block or stimulate the release of specific neurotransmitters. Alternatively, drugs tin can prevent neurotransmitter storage in synaptic vesicles past causing the synaptic vesicle membranes to leak. Drugs that prevent a neurotransmitter from binding to its receptor are called receptor antagonists. For example, drugs used to treat patients with schizophrenia such as haloperidol, chlorpromazine, and clozapine are antagonists at receptors in the brain for dopamine. Other drugs act past binding to a receptor and mimicking the normal neurotransmitter. Such drugs are called receptor agonists. An example of a receptor agonist is morphine, an opiate that mimics effects of the endogenous neurotransmitter β-endorphin to relieve hurting. Other drugs interfere with the deactivation of a neurotransmitter after it has been released, thereby prolonging the action of a neurotransmitter. This can be accomplished past blocking re-uptake or inhibiting degradative enzymes. Lastly, drugs can also prevent an action potential from occurring, blocking neuronal activity throughout the central and peripheral nervous system. Drugs such as tetrodotoxin that block neural activity are typically lethal.

Drugs targeting the neurotransmitter of major systems affect the whole arrangement, which can explain the complication of action of some drugs. Cocaine, for example, blocks the re-uptake of dopamine back into the presynaptic neuron, leaving the neurotransmitter molecules in the synaptic gap for an extended period of time. Since the dopamine remains in the synapse longer, the neurotransmitter continues to demark to the receptors on the postsynaptic neuron, eliciting a pleasurable emotional response. Concrete addiction to cocaine may consequence from prolonged exposure to excess dopamine in the synapses, which leads to the downregulation of some post-synaptic receptors. Subsequently the effects of the drug wear off, an individual can become depressed due to decreased probability of the neurotransmitter bounden to a receptor. Fluoxetine is a selective serotonin re-uptake inhibitor (SSRI), which blocks re-uptake of serotonin by the presynaptic jail cell which increases the amount of serotonin present at the synapse and furthermore allows information technology to remain there longer, providing potential for the effect of naturally released serotonin.^[51] AMPT prevents the conversion of tyrosine to L-DOPA, the precursor to dopamine; reserpine prevents dopamine storage within vesicles; and deprenyl inhibits monoamine oxidase (MAO)-B and thus increases dopamine levels.

Drug-Neurotransmitter Interactions^[52]

Drug	Interacts with:	Receptor Interaction:	Type	Effects
Botulinum Toxin (Botox)	Acetylcholine	–	Adversary	Blocks acetylcholine release in PNS Prevents muscle contractions
Black Widow Spider Venom	Acetylcholine	–	Agonist	Promotes acetylcholine release in PNS Stimulates musculus contractions
Neostigmine	Acetylcholine	–	–	Interferes with acetylcholinerase activity Increases effects of ACh at receptors Used to treat myasthenia gravis
Nicotine	Acetylcholine	Nicotinic (skeletal muscle)	Agonist	Increases ACh activity Increases attending Reinforcing effects
d-tubocurarine	Acetylcholine	Nicotinic (skeletal musculus)	Antagonist	Decreases activity at receptor site
Curare	Acetylcholine	Nicotinic (skeletal muscle)	Antagonist	Decreases ACh activity Prevents muscle contractions
Muscarine	Acetylcholine	Muscarinic (heart and smooth muscle)	Agonist	Increases ACh action Toxic
Atropine	Acetylcholine	Muscarinic (heart and smooth muscle)	Adversary	Blocks educatee constriction Blocks saliva production
Scopolamine (Hyoscine)	Acetylcholine	Muscarinic (heart and smoothen muscle)	Antagonist	Treats motion sickness and postoperative nausea and vomiting
AMPT	Dopamine/norepinephrine	–	–	Inactivates tyrosine hydroxylase and inhibits dopamine production
Reserpine	Dopamine	–	–	Prevents storage of dopamine and other monoamines in synaptic vesicles Causes sedation and depression
Apomorphine	Dopamine	D2 Receptor (presynaptic autoreceptors/postsynaptic receptors)	Antagonist (depression dose)/Straight agonist (high dose)	Low dose: blocks autoreceptors High dose: stimulates postsynaptic receptors
Amphetamine	Dopamine/norepinephrine	–	Indirect agonist	Releases dopamine, noradrenaline, and serotonin Blocks reuptake[32] [33]
Methamphetamine	Dopamine/norepinephrine	–	–	Releases dopamine and noradrenaline Blocks reuptake
Methylphenidate	Dopamine	–	–	Blocks reuptake Enhances attention and impulse control in ADHD
Cocaine	Dopamine	–	Indirect Agonist	Blocks reuptake into presynapse Blocks voltage-dependent sodium channels Tin can be used every bit a topical anesthetic (eye drops)
Deprenyl	Dopamine	–	Agonist	Inhibits MAO-B Prevents destruction of dopamine
Chlorpromazine	Dopamine	D2 Receptors	Antagonist	Blocks D2 receptors Alleviates hallucinations
MPTP	Dopamine	–	–	Results in Parkinson like symptoms
PCPA	Serotonin (5-HT)	–	Antagonist	Disrupts serotonin synthesis by blocking the activity of tryptophan hydroxylase
Ondansetron	Serotonin (5-HT)	v-HTthree receptors	Antagonist	Reduces side effects of chemotherapy and radiation Reduces nausea and airsickness
Buspirone	Serotonin (5-HT)	5-HT1A receptors	Partial Agonist	Treats symptoms of anxiety and depression
Fluoxetine	Serotonin (5-HT)	supports 5-HT reuptake	SSRI	Inhibits reuptake of serotonin Treats low, some anxiety disorders, and OCD[51] Mutual examples: Prozac and Sarafem
Fenfluramine	Serotonin (v-HT)	–	–	Causes release of serotonin Inhibits reuptake of serotonin Used equally an appetite suppressant
Lysergic acrid diethylamide	Serotonin (5-HT)	Post-synaptic 5-HT2A receptors	Direct Agonist	Produces visual perception distortions Stimulates five-HT2A receptors in forebrain
Methylenedioxymethamphetamine (MDMA)	Serotonin (5-HT)/ norepinphrine	–	–	Stimulates release of serotonin and norepinephrine and inhibits the reuptake Causes excitatory and hallucinogenic furnishings
Strychnine	Glycine	–	Antagonist	Causes severe muscle spasms[53]
Diphenhydramine	Histamine			Crosses blood encephalon bulwark to cause drowsiness
Tetrahydrocannabinol (THC)	Endocannabinoids	Cannabinoid (CB) receptors	Agonist	Produces analgesia and sedation Increases appetite Cognitive effects
Rimonabant	Endocannabinoids	Cannabinoid (CB) receptors	Antagonist	Suppresses appetite Used in smoking cessation
MAFP	Endocannabinoids	–	–	Inhibits FAAH Used in enquiry to increase cannabinoid organisation activity
AM1172	Endocannabinoids	–	–	Blocks cannabinoid reuptake Used in research to increase cannabinoid system activity
Anandamide (endogenous)	–	Cannabinoid (CB) receptors; 5-HTthree receptors	–	Reduce nausea and vomiting
Caffeine	Adenosine	Adenosine receptors	Antagonist	Blocks adenosine receptors Increases wakefulness
PCP	Glutamate	NMDA receptor	Indirect Antagonist	Blocks PCP bounden site Prevents calcium ions from entering neurons Impairs learning
AP5	Glutamate	NMDA receptor	Antagonist	Blocks glutamate bounden site on NMDA receptor Impairs synaptic plasticity and certain forms of learning
Ketamine	Glutamate	NMDA receptor	Adversary	Used as anesthesia Induces trance-similar state, helps with hurting relief and sedation
NMDA	Glutamate	NMDA receptor	Agonist	Used in research to written report NMDA receptor Ionotropic receptor
AMPA	Glutamate	AMPA receptor	Agonist	Used in research to written report AMPA receptor Ionotropic receptor
Allyglycine	GABA	–	–	Inhibits GABA synthesis Causes seizures
Muscimol	GABA	GABA receptor	Agonist	Causes sedation
Bicuculine	GABA	GABA receptor	Adversary	Causes Seizures
Benzodiazepines	GABA	GABAA receptor	Indirect agonists	Anxiolytic, sedation, memory impairment, muscle relaxation
Barbiturates	GABA	GABAA receptor	Indirect agonists	Sedation, retention harm, muscle relaxation
Booze	GABA	GABA receptor	Indirect agonist	Sedation, retentiveness damage, musculus relaxation
Picrotoxin	GABA	GABAA receptor	Indirect adversary	High doses cause seizures
Tiagabine	GABA	–	Antagonist	GABA transporter antagonist Increment availability of GABA Reduces the likelihood of seizures
Moclobemide	Norepinephrine	–	Agonist	Blocks MAO-A to treat depression
Idazoxan	Norepinephrine	alpha-ii adrenergic autoreceptors	Agonist	Blocks blastoff-2 autoreceptors Used to study norepinephrine organisation
Fusaric acrid	Norepinephrine	–	–	Inhibits activeness of dopamine beta-hydroxylase which blocks the product of norepinephrine Used to written report norepinephrine system without affecting dopamine system
Opiates (Opium, morphine, heroin, and oxycodone)	Opioids	Opioid receptor[54]	Agonists	Analgesia, sedation, and reinforcing furnishings
Naloxone	Opioids	–	Adversary	Reverses opiate intoxication or overdose symptoms (i.east. bug with breathing)

Agonists [edit]

This section needs expansion with: coverage of total agonists and their distinction from partial agonist and inverse agonist.. You lot can help by adding to it. (August 2015)

An agonist is a chemical capable of bounden to a receptor, such every bit a neurotransmitter receptor, and initiating the same reaction typically produced by the bounden of the endogenous substance.^[55] An agonist of a neurotransmitter volition thus initiate the same receptor response as the transmitter. In neurons, an agonist drug may activate neurotransmitter receptors either directly or indirectly. Direct-binding agonists can be farther characterized as full agonists, partial agonists, inverse agonists.^{[56] [57]}

Straight agonists act similar to a neurotransmitter by binding straight to its associated receptor site(south), which may be located on the presynaptic neuron or postsynaptic neuron, or both.^[58] Typically, neurotransmitter receptors are located on the postsynaptic neuron, while neurotransmitter autoreceptors are located on the presynaptic neuron, as is the case for monoamine neurotransmitters;^[32] in some cases, a neurotransmitter utilizes retrograde neurotransmission, a type of feedback signaling in neurons where the neurotransmitter is released postsynaptically and binds to target receptors located on the presynaptic neuron.^{[59] [annotation 1]} Nicotine, a compound found in tobacco, is a straight agonist of most nicotinic acetylcholine receptors, mainly located in cholinergic neurons.^[54] Opiates, such every bit morphine, heroin, hydrocodone, oxycodone, codeine, and methadone, are μ-opioid receptor agonists; this action mediates their euphoriant and pain relieving properties.^[54]

Indirect agonists increase the binding of neurotransmitters at their target receptors by stimulating the release or preventing the reuptake of neurotransmitters.^[58] Some indirect agonists trigger neurotransmitter release and prevent neurotransmitter reuptake. Amphetamine, for example, is an indirect agonist of postsynaptic dopamine, norepinephrine, and serotonin receptors in each their respective neurons;^{[32] [33]} it produces both neurotransmitter release into the presynaptic neuron and after the synaptic scissure and prevents their reuptake from the synaptic fissure by activating TAAR1, a presynaptic K protein-coupled receptor, and binding to a site on VMAT2, a blazon of monoamine transporter located on synaptic vesicles inside monoamine neurons.^{[32] [33]}

Antagonists [edit]

An antagonist is a chemical that acts within the torso to reduce the physiological activity of another chemic substance (as an opiate); peculiarly one that opposes the action on the nervous system of a drug or a substance occurring naturally in the trunk by combining with and blocking its nervous receptor.^[lx]

In that location are two primary types of antagonist: direct-acting Antagonist and indirect-interim Antagonists:

1. Direct-acting antagonist- which takes up space nowadays on receptors which are otherwise taken up past neurotransmitters themselves. This results in neurotransmitters existence blocked from binding to the receptors. The well-nigh common is chosen Atropine.
2. Indirect-acting antagonist- drugs that inhibit the release/production of neurotransmitters (e.thou., Reserpine).

Drug antagonists [edit]

An antagonist drug is one that attaches (or binds) to a site chosen a receptor without activating that receptor to produce a biological response. It is therefore said to have no intrinsic activity. An adversary may also exist called a receptor "blocker" because they cake the outcome of an agonist at the site. The pharmacological furnishings of an antagonist, therefore, upshot in preventing the corresponding receptor site's agonists (e.1000., drugs, hormones, neurotransmitters) from bounden to and activating information technology. Antagonists may exist "competitive" or "irreversible".

A competitive antagonist competes with an agonist for binding to the receptor. Equally the concentration of adversary increases, the binding of the agonist is progressively inhibited, resulting in a subtract in the physiological response. Loftier concentration of an adversary can completely inhibit the response. This inhibition can exist reversed, however, by an increment of the concentration of the agonist, since the agonist and antagonist compete for binding to the receptor. Competitive antagonists, therefore, tin exist characterized as shifting the dose–response relationship for the agonist to the right. In the presence of a competitive antagonist, it takes an increased concentration of the agonist to produce the aforementioned response observed in the absence of the antagonist.

An irreversible adversary binds so strongly to the receptor every bit to return the receptor unavailable for bounden to the agonist. Irreversible antagonists may even form covalent chemical bonds with the receptor. In either example, if the concentration of the irreversible adversary is high enough, the number of unbound receptors remaining for agonist binding may be so low that fifty-fifty loftier concentrations of the agonist do not produce the maximum biological response.^[61]

Precursors [edit]

While intake of neurotransmitter precursors does increase neurotransmitter synthesis, evidence is mixed as to whether neurotransmitter release and postsynaptic receptor firing is increased. Even with increased neurotransmitter release, it is unclear whether this will outcome in a long-term increase in neurotransmitter signal strength, since the nervous arrangement can adapt to changes such equally increased neurotransmitter synthesis and may therefore maintain constant firing.^{[65] [ unreliable medical source? ]} Some neurotransmitters may have a function in depression and there is some evidence to suggest that intake of precursors of these neurotransmitters may exist useful in the handling of mild and moderate depression.^{[65] [ unreliable medical source? ] [66]}

Catecholamine and trace amine precursors [edit]

L-DOPA, a precursor of dopamine that crosses the claret–brain barrier, is used in the treatment of Parkinson's illness. For depressed patients where depression activeness of the neurotransmitter norepinephrine is implicated, there is only little bear witness for benefit of neurotransmitter precursor assistants. Fifty-phenylalanine and 50-tyrosine are both precursors for dopamine, norepinephrine, and epinephrine. These conversions crave vitamin B6, vitamin C, and S-adenosylmethionine. A few studies suggest potential antidepressant furnishings of L-phenylalanine and L-tyrosine, but there is much room for further research in this area.^{[65] [ unreliable medical source? ]}

Serotonin precursors [edit]

Administration of L-tryptophan, a precursor for serotonin, is seen to double the product of serotonin in the encephalon. It is significantly more effective than a placebo in the handling of mild and moderate low.^{[65] [ unreliable medical source? ]} This conversion requires vitamin C.^[21] 5-hydroxytryptophan (5-HTP), too a precursor for serotonin, is more constructive than a placebo.^{[65] [ unreliable medical source? ]}

Diseases and disorders [edit]

Diseases and disorders may also impact specific neurotransmitter systems. The following are disorders involved in either an increase, decrease, or imbalance of certain neurotransmitters.

Dopamine:

For example, problems in producing dopamine (mainly in the substantia nigra) can result in Parkinson'south disease, a disorder that affects a person'due south ability to move as they want to, resulting in stiffness, tremors or shaking, and other symptoms. Some studies suggest that having too piffling or too much dopamine or problems using dopamine in the thinking and feeling regions of the brain may play a role in disorders like schizophrenia or attention deficit hyperactivity disorder (ADHD). Dopamine is also involved in habit and drug use, every bit virtually recreational drugs crusade an influx of dopamine in the encephalon (especially opioid and methamphetamines) that produces a pleasurable feeling, which is why users constantly crave drugs.

Serotonin:

Similarly, after some enquiry suggested that drugs that cake the recycling, or reuptake, of serotonin seemed to help some people diagnosed with depression, it was theorized that people with depression might accept lower-than-normal serotonin levels. Though widely popularized, this theory was not borne out in subsequent research.^[67] Therefore, selective serotonin reuptake inhibitors (SSRIs) are used to increment the amounts of serotonin in synapses.

Glutamate:

Furthermore, problems with producing or using glutamate have been suggestively and tentatively linked to many mental disorders, including autism, obsessive compulsive disorder (OCD), schizophrenia, and depression.^[68] Having too much glutamate has been linked to neurological diseases such as Parkinson's disease, multiple sclerosis, Alzheimer's affliction, stroke, and ALS (amyotrophic lateral sclerosis).^[69]

CAPON Binds Nitric Oxide Synthase, Regulating NMDA Receptor–Mediated Glutamate Neurotransmission

Neurotransmitter imbalance [edit]

Generally, there are no scientifically established "norms" for advisable levels or "balances" of different neurotransmitters. It is in most cases pragmatically impossible to even measure levels of neurotransmitters in a brain or body at any distinct moments in time. Neurotransmitters regulate each other's release, and weak consistent imbalances in this mutual regulation were linked to temperament in healthy people .^{[lxx] [71] [72] [73] [74]} Strong imbalances or disruptions to neurotransmitter systems accept been associated with many diseases and mental disorders. These include Parkinson's, depression, insomnia, Attention Deficit Hyperactivity Disorder (ADHD), anxiety, memory loss, dramatic changes in weight and addictions. Chronic physical or emotional stress can be a correspondent to neurotransmitter system changes. Genetics also plays a role in neurotransmitter activities. Apart from recreational use, medications that directly and indirectly interact with i or more transmitter or its receptor are unremarkably prescribed for psychiatric and psychological problems. Notably, drugs interacting with serotonin and norepinephrine are prescribed to patients with issues such as low and anxiety—though the notion that there is much solid medical evidence to support such interventions has been widely criticized.^[75] Studies shown that dopamine imbalance has an influence on multiple sclerosis and other neurological disorders.^[76]

See also [edit]

• BK channel#Cellular level
• Osculation-and-run fusion
• Natural neuroactive substance
• Neuroendocrine
• Neuroendocrinology
• Neuropsychopharmacology
• Neurotransmitter analog
• Neurotransmitter release
• Neural pathway
• Neuromodulation

Notes [edit]

1. ^ In the cardinal nervous system, anandamide other endocannabinoids use retrograde neurotransmission, since their release is postsynaptic, while their target receptor, cannabinoid receptor 1 (CB1), is presynaptic.^[59] The cannabis plant contains Δ^ix-tetrahydrocannabinol, which is a direct agonist at CB1.^[59]

1. ^ GABA is a non-proteinogenic amino acrid

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34. ^ ^{a b c} Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 6: Widely Projecting Systems: Monoamines, Acetylcholine, and Orexin". In Sydor A, Brown RY (eds.). Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (second ed.). New York: McGraw-Hill Medical. p. 155. ISBN9780071481274. Different subregions of the VTA receive glutamatergic inputs from the prefrontal cortex, orexinergic inputs from the lateral hypothalamus, cholinergic and also glutamatergic and GABAergic inputs from the laterodorsal tegmental nucleus and pedunculopontine nucleus, noradrenergic inputs from the locus ceruleus, serotonergic inputs from the raphe nuclei, and GABAergic inputs from the nucleus accumbens and ventral pallidum.
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36. ^ ^{a b c d} Rang HP (2003). Pharmacology. Edinburgh: Churchill Livingstone. pp. 474 for noradrenaline organization, page 476 for dopamine system, page 480 for serotonin organization and folio 483 for cholinergic system. ISBN978-0-443-07145-four.
37. ^ ^{a b c d e} Iwańczuk W, Guźniczak P (2015). "Neurophysiological foundations of sleep, arousal, awareness and consciousness phenomena. Part 1". Anaesthesiology Intensive Therapy. 47 (2): 162–vii. doi:10.5603/AIT.2015.0015. PMID 25940332. The ascending reticular activating system (ARAS) is responsible for a sustained wakefulness state. ... The thalamic project is dominated past cholinergic neurons originating from the pedunculopontine tegmental nucleus of pons and midbrain (PPT) and laterodorsal tegmental nucleus of pons and midbrain (LDT) nuclei [17, 18]. The hypothalamic projection involves noradrenergic neurons of the locus coeruleus (LC) and serotoninergic neurons of the dorsal and median raphe nuclei (DR), which pass through the lateral hypothalamus and reach axons of the histaminergic tubero-mamillary nucleus (TMN), together forming a pathway extending into the forebrain, cortex and hippocampus. Cortical arousal also takes advantage of dopaminergic neurons of the substantia nigra (SN), ventral tegmenti area (VTA) and the periaqueductal gray area (PAG). Fewer cholinergic neurons of the pons and midbrain send projections to the forebrain along the ventral pathway, bypassing the thalamus [19, 20].
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External links [edit]

• Molecular Cell Biology. 4th edition. Section 21.4: Neurotransmitters, Synapses, and Impulse Manual
• Molecular Expressions Photo Gallery: The Neurotransmitter Drove
• Encephalon Neurotransmitters
• Endogenous Neuroactive Extracellular Point Transducers
• Neurotransmitter at the US National Library of Medicine Medical Subject Headings (MeSH)
• neuroscience for kids website
• encephalon explorer website

gotchvailes.blogspot.com

Source: https://en.wikipedia.org/wiki/Neurotransmitter

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