# Synapses and Neurotransmitters > FMGE Physiology notes on synapses and neurotransmitters: transmitter synthesis pathways, receptors, toxins and pharmacology bridges tested by NBE. - Canonical URL: https://prepelephant.com/topics/fmge/physiology/synapse-neurotransmitters-fmge - Exam / course: FMGE · Subject: Physiology - Publisher: PrepElephant (https://prepelephant.com) — Prepared and reviewed by the PrepElephant Academic Review Team - First published: 2026-10-02 - Last updated: 2026-10-02 - How to cite: "Synapses and Neurotransmitters", PrepElephant, https://prepelephant.com/topics/fmge/physiology/synapse-neurotransmitters-fmge ## Direct answer Chemical synapses, 20-30 nanometres wide, convert presynaptic calcium entry into quantal transmitter release with a 0.5 millisecond synaptic delay, while electrical synapses — gap junctions only 2-3 nanometres across — transmit instantly and bidirectionally. Acetylcholine synthesis joins choline and acetyl-CoA through choline acetyltransferase, with high-affinity choline uptake the rate-limiting step (hemicholinium blocks it, vesamicol blocks vesicular storage); noradrenaline synthesis runs tyrosine to DOPA through tyrosine hydroxylase — the rate-limiting enzyme — to dopamine and noradrenaline, with phenylethanolamine-N-methyltransferase, induced by cortisol, adding the methyl group for adrenaline in the medulla. The transmitter roster is functional: glutamate is the chief excitatory transmitter of the central nervous system, GABA the chief inhibitory one (GABA-A ionotropic chloride, GABA-B metabotropic, baclofen), glycine the cord's inhibitor that strychnine antagonises, serotonin modulates mood, nitric oxide diffuses back as a retrograde messenger, and dopamine inhibits prolactin while vasodilating the kidney through D1 receptors. Degradation and reuptake, not synthesis, are where the pharmacology bites. ## What you must remember - **Synapse mechanics:** calcium entry through voltage-gated channels is the only release trigger; the SNARE complex (synaptobrevin, syntaxin, SNAP-25) fuses vesicles; 0.5 ms delay estimates chain neurons — 2 ms implies about four synapses. - **Cholinergic pharmacology points:** organophosphates irreversibly phosphorylate acetylcholinesterase (treat with atropine plus pralidoxime before the enzyme ages); botulinum toxin cleaves SNAREs blocking release; hemicholinium stops choline uptake; vesamicol stops vesicular storage. - **Catecholamine cascade:** tyrosine hydroxylase is rate-limiting (inhibited by alpha-methyltyrosine); dopamine beta-hydroxylase makes noradrenaline inside vesicles; PNMT needs cortisol's induction — hence the adrenal medulla's 80:20 adrenaline output; reserpine empties vesicles through VMAT blockade; cocaine and tricyclics block reuptake; metabolism through MAO and COMT yields VMA and metanephrines, the phaeochromocytoma analytes. - **Amino acid transmitters:** glutamate chief excitatory — NMDA receptors need glutamate plus glycine plus depolarisation to dislodge magnesium, and their calcium influx underlies excitotoxicity in stroke; GABA chief inhibitory, synthesised by glutamic acid decarboxylase with pyridoxine (vitamin B6) as cofactor — the reason isoniazid-induced B6 depletion causes seizures. - **Modulators:** serotonin (raphe nuclei, about 90 per cent of body serotonin in enterochromaffin cells) with seven receptor families — 5-HT3 ionotropic, the rest metabotropic; dopamine mesolimbic (reward), tuberoinfundibular (prolactin inhibition), and nigrostriatal (Parkinson's); nitric oxide synthesised by nitric oxide synthase from arginine, acting through cGMP — sildenafil's target downstream. - **Receptor families:** ionotropic (nicotinic, GABA-A, glycine, 5-HT3, glutamate) are fast channels; metabotropic (muscarinic M1-M5, adrenergic, GABA-B, dopamine) are G-protein-coupled and slower. - **Co-transmission:** small-molecule transmitters and neuropeptides share terminals, released at different firing frequencies — the autonomic co-release of ATP and neuropeptide Y with noradrenaline being the example. ## One acetylcholine vesicle, traced Follow a quantum of acetylcholine at the neuromuscular junction. Choline is pumped into the terminal (the step hemicholinium kills), choline acetyltransferase acetylates it, and the vesicular transporter packs it — vesamicol's target. An arriving action potential opens calcium channels, calcium binds synaptotagmin, SNARE complexes fuse the vesicle, and roughly 5,000-10,000 molecules spray across the 20-30 nanometre cleft in under a millisecond. Two acetylcholine molecules open each nicotinic receptor; the end-plate potential fires. Acetylcholinesterase in the cleft hydrolyses the transmitter within a millisecond, and choline is recycled. Now break the loop pharmacologically: organophosphates leave transmitter undegraded — muscarinic crisis (constricted pupils, secretions, bradycardia) plus nicotinic weakness, treated with atropine plus pralidoxime before the enzyme ages; botulinum stops fusion (flaccid paralysis); myasthenia gravis attacks the receptors (fatigable weakness improving with edrophonium); and neostigmine inhibits the esterase, amplifying each quantum — its myasthenia rationale. ## The pharmacology bridge examiners love The bridge from physiology to pharmacology is where FMGE marks concentrate. Isoniazid depletes pyridoxine, glutamic acid decarboxylase fails, GABA synthesis falls, and seizures follow — prevented by routine B6 supplementation in the Indian tuberculosis programme. L-Dopa crosses the blood-brain barrier (dopamine cannot), given with carbidopa to block peripheral decarboxylation. Baclofen, a GABA-B agonist, is the antispastic; benzodiazepines and barbiturates act at different GABA-A sites to prolong chloride opening. Fluoxetine blocks serotonin reuptake, and the triptans are 5-HT1B/1D agonists. Nitric oxide explains nitroglycerine's vasodilatation through cGMP, and sildenafil's potentiation of the same messenger — hence the contraindicated nitrate combination. Every one of these drug facts is a physiology fact wearing a prescription. ## Frequently asked questions ### What is the rate-limiting step in catecholamine synthesis? Tyrosine hydroxylase converting tyrosine to DOPA; choline uptake plays the equivalent rate-limiting role for acetylcholine, which hemicholinium blocks. ### Why must pyridoxine be given with isoniazid? Isoniazid induces pyridoxine depletion, and pyridoxine is the cofactor for glutamic acid decarboxylase in GABA synthesis — deficiency causes seizures and peripheral neuropathy. ### How do GABA-A and GABA-B receptors differ? GABA-A is an ionotropic chloride channel (benzodiazepine and barbiturate sites) mediating fast inhibition; GABA-B is a G-protein-coupled potassium channel opener, agonised by baclofen. ### What is the mechanism of organophosphate poisoning and its treatment? Irreversible acetylcholinesterase inhibition causes cholinergic excess; atropine blocks muscarinic effects and pralidoxime reactivates the enzyme if given before it ages. ### Why is nitric oxide called a retrograde messenger? Synthesised postsynaptically, it diffuses back to the presynaptic terminal and raises cGMP, enhancing transmitter release — the unusual direction that underlies synaptic plasticity.