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[Physiology](https://durgical.com/en/physiology/) · [Neurophysiology](https://durgical.com/en/physiology/#s-neuro)

# The main neurotransmitters

- Table to know
- Exam priority: medium

Neurons talk with a small set of chemicals; each one has its own jobs, its source nuclei and the diseases that follow when it fails.

Updated 2026-11-01

Also called: Neuromodulators, Neuropeptides

## Key points

- Glutamate acts on AMPA and NMDA receptors; NMDA needs glycine as co-agonist and depolarization to expel its Mg²⁺ plug. Excess glutamate kills neurons (excitotoxicity) in stroke and seizures.
- GABA_A is a Cl⁻ channel and the site of action of benzodiazepines, barbiturates and alcohol; GABA_B is a G protein receptor.
- Glycine inhibits in the cord and brainstem; tetanus toxin and strychnine block it, causing spasms.
- Source nuclei: dopamine – substantia nigra and ventral tegmental area; norepinephrine – locus coeruleus; serotonin – raphe; acetylcholine – nucleus basalis of Meynert; histamine – tuberomammillary nucleus.
- Alzheimer disease: early loss of cholinergic neurons of the nucleus basalis; Parkinson disease: loss of nigral dopamine.
- Synthesis: dopamine and norepinephrine from tyrosine (tyrosine hydroxylase is rate-limiting); serotonin from tryptophan; GABA from glutamate by glutamate decarboxylase (needs vitamin B6).

## What it is

Small-molecule transmitters (acetylcholine, amines, amino acids) are made in the terminal and act fast; neuropeptides are made in the cell body, released in small amounts and act slowly and for longer. Glutamate is the main excitatory transmitter of the brain, GABA the main inhibitory one and glycine the inhibitory one of the spinal cord and brainstem. The monoamines (dopamine, norepinephrine, serotonin, histamine) come from small brainstem and hypothalamic nuclei that project widely and set arousal, mood and motivation.

## Transmitters, sources and receptors

| Transmitter | Main source | Receptors | Role and disorders |
| --- | --- | --- | --- |
| Glutamate | Widespread (cortex, hippocampus) | AMPA, NMDA, kainate, mGluR | Excitation, memory (LTP); excitotoxicity in stroke |
| [GABA](https://durgical.com/en/conditions/epilepsy-and-seizures/) | Interneurons, striatum, cerebellar Purkinje cells | GABA_A (Cl⁻), GABA_B | Inhibition; too little favours seizures |
| Glycine | Cord and brainstem interneurons | Glycine receptor (Cl⁻) | Inhibition; blocked by tetanus toxin and strychnine |
| [Acetylcholine](https://durgical.com/en/conditions/alzheimer-disease/) | Nucleus basalis, motor and autonomic neurons | Nicotinic, muscarinic | Attention, memory, muscle; lost early in Alzheimer disease |
| [Dopamine](https://durgical.com/en/conditions/parkinson-disease/) | Substantia nigra, ventral tegmental area, hypothalamus | D1–D5 | Movement, reward; inhibits prolactin; lost in Parkinson disease |
| Norepinephrine | Locus coeruleus, sympathetic postganglionic neurons | α, β | Arousal, attention; implicated in depression |
| Serotonin | Raphe nuclei | 5-HT1 to 5-HT7 | Mood, sleep, appetite, pain modulation |
| Histamine | Tuberomammillary nucleus (hypothalamus) | H1–H3 | Wakefulness; first-generation antihistamines sedate |
| Neuropeptides (substance P, enkephalins, endorphins) | Dorsal horn, hypothalamus, periaqueductal gray | NK1; μ, δ, κ opioid | Pain transmission and its modulation |

## Clinical notes

- Tetanus (Clostridium tetani toxin) blocks glycine and GABA release in the cord: trismus, opisthotonus, painful spasms.
- Alcohol or benzodiazepine withdrawal leaves glutamate unopposed: tremor, agitation and seizures.
- Antipsychotics that block D2 receptors cause parkinsonism (striatum) and high prolactin (pituitary).

## Memory aid

Glutamate is the gas pedal, GABA the brake in the brain, glycine the brake in the cord.

## Test yourself

Think of the answer, then tap the question to see it.

## Why does the NMDA receptor act as a coincidence detector in memory formation?

It opens only when glutamate is bound and the membrane is already depolarized enough to expel its Mg²⁺ plug. Then Ca²⁺ enters and triggers long-term potentiation.

## Why do D2-blocking drugs raise prolactin?

Hypothalamic dopamine reaches the pituitary through portal blood and inhibits lactotrophs through D2 receptors. Blocking them removes the brake, so prolactin rises (galactorrhea, amenorrhea).

## Benzodiazepines and alcohol both enhance GABA. Why is stopping them suddenly dangerous?

Chronic use reduces GABA_A function and increases glutamate signalling. Abrupt withdrawal leaves excitation unopposed, causing tremor, agitation and seizures.

## Why do first-generation antihistamines cause drowsiness?

They cross the blood–brain barrier and block H1 receptors of the tuberomammillary histamine neurons, which keep the cortex awake.

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## Related topics

- [Synaptic transmission](https://durgical.com/en/physiology/synaptic-transmission/)
- [Basal ganglia and movement control](https://durgical.com/en/physiology/basal-ganglia-and-movement-control/)
- [Adrenergic and cholinergic receptors](https://durgical.com/en/physiology/adrenergic-and-cholinergic-receptors/)
- [Wakefulness, sleep, the EEG and seizures](https://durgical.com/en/physiology/wakefulness-sleep-the-eeg-and-seizures/)
- [The limbic system, emotion and reward](https://durgical.com/en/physiology/the-limbic-system-emotion-and-reward/)
- [Pain and temperature: pathways and modulation](https://durgical.com/en/physiology/pain-and-temperature-pathways-and-modulation/)

## Related conditions

- [Parkinson disease](https://durgical.com/en/conditions/parkinson-disease/)
- [Alzheimer disease](https://durgical.com/en/conditions/alzheimer-disease/)
- [Epilepsy and seizures](https://durgical.com/en/conditions/epilepsy-and-seizures/)
- [Huntington disease](https://durgical.com/en/conditions/huntington-disease/)

## In Biochemistry

- [Glutamate (glutamic acid)](https://durgical.com/en/biochemistry/molecules/glutamate/)
- [Catecholamines: synthesis and breakdown](https://durgical.com/en/biochemistry/topics/catecholamines-synthesis-and-breakdown/)
- [Molecules derived from amino acids](https://durgical.com/en/biochemistry/topics/molecules-derived-from-amino-acids/)
- [Tyrosine](https://durgical.com/en/biochemistry/molecules/tyrosine/)
- [Tryptophan](https://durgical.com/en/biochemistry/molecules/tryptophan/)

## In Pharmacology

- [Opioids and antagonists](https://durgical.com/en/pharmacology/classes/opioids-and-antagonists/)

[← All of physiology](https://durgical.com/en/physiology/)

Educational physiology content; not a diagnostic or treatment guide and no substitute for a health professional's advice. Values are approximate references. No doses are given.

Sources: [12.5 Communication Between Neurons](https://openstax.org/books/anatomy-and-physiology-2e/pages/12-5-communication-between-neurons) (OpenStax (Rice University), 2022); [Parkinson Disease](https://www.ncbi.nlm.nih.gov/books/NBK470193/) (StatPearls (NCBI Bookshelf), 2023); Hall JE. Guyton and Hall Textbook of Medical Physiology, 13th ed. (ch. 46). Reference book used to check facts; its text and figures are not reproduced (Elsevier, 2016).

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