The synaptic cycle gives us five drug-target points. Memorize this map; it will let you predict what any new psychiatric medication does mechanistically from the step it targets.
Target 1: Synthesis. Give a precursor or activate the synthetic pathway. Levodopa for Parkinson's disease is the canonical example — the dopamine precursor, given orally, crosses the blood-brain barrier and is converted to dopamine by surviving neurons. We discussed this in Stage 5. No drug class is named specifically for this mechanism, but it remains one of the most clinically important interventions in neurology.
Target 2: Release. Make presynaptic terminals release more neurotransmitter. Amphetamines work this way — they reverse the dopamine and norepinephrine transporters, dumping neurotransmitter into the synapse. Methamphetamine works similarly with stronger central effects. These drugs have therapeutic use in ADHD and narcolepsy and significant abuse potential because they massively elevate synaptic dopamine.
Target 3: Reuptake blockade. Block the transporter that normally recycles neurotransmitter, and it stays in the synapse longer. This is the largest single drug class in psychiatry. SSRIs block serotonin reuptake. SNRIs block serotonin and norepinephrine reuptake. Bupropion blocks dopamine and norepinephrine reuptake. Atomoxetine blocks norepinephrine reuptake. Cocaine blocks dopamine, norepinephrine, and serotonin reuptake all at once — which is why cocaine produces stimulant plus mood effects simultaneously.
Target 4: Breakdown inhibition. Block the enzymes that destroy neurotransmitter. Monoamine oxidase inhibitors (MAOIs) — phenelzine, tranylcypromine, isocarboxazid, selegiline — prevent enzymatic breakdown of dopamine, norepinephrine, and serotonin, raising levels of all three. Cholinesterase inhibitors like donepezil prevent the breakdown of acetylcholine, which is why they are used in Alzheimer's disease.
Target 5: Receptor binding. Activate or block the receptor directly. Antipsychotics are D2 antagonists. Buprenorphine is a partial mu-opioid receptor agonist. Naltrexone is a mu-opioid receptor antagonist. Benzodiazepines are GABA-A receptor positive allosteric modulators. The receptor itself can be the drug target through many different mechanisms, which we will visit in the receptor concepts.
Most psychiatric medications target one step strongly with minor effects at others. SSRIs primarily block reuptake but at higher doses begin affecting other transporters. Antipsychotics primarily block D2 but also affect 5-HT2A, H1 (histamine), M1 (muscarinic), and alpha-1 receptors to varying degrees. The receptor profile of a medication predicts not just its therapeutic effect but its side effect profile.
Hold the five-target map. When you see a new psychiatric medication, ask: which step does it target? The answer locates the drug in this map and gives you a starting point for predicting both its therapeutic and adverse effects.