Every classical neurotransmitter goes through the same five-step cycle at every synapse, and every psychotropic medication intervenes at one of these five steps. Memorize the cycle, because it gives you a complete map of where any psychiatric drug acts.
Step 1: Synthesis. The neurotransmitter is made inside the presynaptic neuron from precursors. Dopamine is made from tyrosine via DOPA. Serotonin is made from tryptophan via 5-hydroxytryptophan. GABA is made from glutamate. Acetylcholine is made from choline and acetyl-CoA. Each pathway has rate-limiting enzymes — for dopamine, tyrosine hydroxylase; for serotonin, tryptophan hydroxylase — that can be regulated up or down.
Step 2: Release. The synthesized neurotransmitter is packaged into synaptic vesicles inside the axon terminal. When an action potential arrives, voltage-gated calcium channels open, calcium flows in, and vesicles fuse with the presynaptic membrane, releasing their contents into the synaptic cleft.
Step 3: Receptor binding. Neurotransmitter molecules diffuse across the synaptic cleft and bind receptors on the postsynaptic membrane. The receptors are typically either ionotropic (ion channels that open directly upon binding) or metabotropic (G-protein-coupled receptors that trigger intracellular cascades). Receptor binding is the step that produces the actual postsynaptic effect.
Step 4: Reuptake. The neurotransmitter is recycled. Specific transporter proteins on the presynaptic membrane pump the neurotransmitter back into the presynaptic neuron, where it can be repackaged into vesicles and released again. There are specific transporters for dopamine (DAT), norepinephrine (NET), serotonin (SERT), and other neurotransmitters.
Step 5: Breakdown. Some neurotransmitter does not get recycled and is instead degraded by enzymes. Monoamine oxidase (MAO) breaks down dopamine, norepinephrine, and serotonin. Catechol-O-methyltransferase (COMT) breaks down catecholamines. Acetylcholinesterase rapidly breaks down acetylcholine at the synapse.
These five steps are five drug targets. Every psychiatric medication intervenes at one (or sometimes more) of these steps to alter the strength or duration of neurotransmission. Levodopa enhances synthesis. Amphetamine enhances release. SSRIs block reuptake. MAOIs inhibit breakdown. Haloperidol blocks the receptor. We will visit each class in the next concepts.
Hold the cycle. Synthesis, release, binding, reuptake, breakdown. Five steps. Five drug-target categories. This is the molecular grammar of psychopharmacology.