Action of neurotransmitters and neurotransmission

Synaptic transmission

Chemical synaptic transmission: presynaptic action potential -> voltage-gated Ca2+ channel opening -> vesicle fusion -> neurotransmitter release -> postsynaptic receptor binding -> ionotropic (fast, direct ion flux) or metabotropic (slow, G-protein coupled) response
Each major neurotransmitter system maps to distinct disease states and drug targets - the physiological basis for most of clinical neuropharmacology

Neurotransmitter	Key receptor(s)	Clinical relevance
Glutamate	NMDA, AMPA (ionotropic)	Excitotoxicity in stroke/status epilepticus
GABA	GABA-A (ionotropic, Cl-), GABA-B (metabotropic)	Benzodiazepines/barbiturates (GABA-A); baclofen (GABA-B)
Dopamine	D1-D5 (all metabotropic)	Parkinson's disease (nigrostriatal loss), antipsychotics (D2 blockade)
Acetylcholine	Nicotinic (ionotropic), muscarinic (metabotropic)	Myasthenia gravis (nicotinic at NMJ), Alzheimer's disease (cholinesterase inhibitors)
Serotonin	5-HT1-7 (mostly metabotropic, 5-HT3 ionotropic)	Depression (SSRIs), serotonin syndrome
Noradrenaline	alpha/beta (metabotropic)	Autonomic function, ADHD, depression

Termination of signal determines drug targets: reuptake (SSRIs - serotonin transporter; cocaine - dopamine/noradrenaline transporter), enzymatic degradation (MAO inhibitors - monoamines; acetylcholinesterase inhibitors - ACh)
Ionotropic receptors act in milliseconds (fast synaptic transmission); metabotropic receptors act over seconds-minutes (modulatory, second-messenger mediated) - explains why NMDA-receptor antagonists (ketamine) act rapidly while SSRIs take weeks

Parkinson's disease, myasthenia gravis, epilepsy/excitotoxicity, major depressive disorder, serotonin syndrome, neuroleptic malignant syndrome

Most CNS drug classes are named for which step of this pathway they act on (synthesis, release, receptor, reuptake, degradation) - a useful organising framework for pharmacology recall

4 more sections, plus exam facts

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