Dopamine has at least five known receptor subtypes (D1 through D5), but for clinical neuropsychiatry the two that matter most are D1 and D2. They have opposite second-messenger effects, opposite distributions across the basal ganglia pathways, and opposite roles in clinical pharmacology.
D1 receptors are coupled to Gs proteins. When dopamine binds, the receptor activates adenylate cyclase, increasing intracellular cyclic AMP. The net effect on the postsynaptic neuron is excitatory. D1 receptors are concentrated on direct-pathway striatal neurons, where they promote firing and therefore promote movement.
D2 receptors are coupled to Gi proteins. When dopamine binds, the receptor inhibits adenylate cyclase, decreasing intracellular cyclic AMP. The net effect on the postsynaptic neuron is inhibitory. D2 receptors are concentrated on indirect-pathway striatal neurons, where dopamine inhibits firing and therefore disinhibits movement.
Both pathways converge on the same conclusion: dopamine promotes movement. Whether through direct-pathway excitation via D1 or indirect-pathway disinhibition via D2, the net effect of nigrostriatal dopamine is to open the gate for cortical motor programs.
Clinically, the most important manipulation is D2 blockade. All antipsychotic medications, without exception, block D2 receptors to some degree. The result is more indirect-pathway firing, more inhibition of thalamus, less cortical motor output — and the patient develops the bradykinesia, rigidity, and tremor of iatrogenic Parkinsonism, also called extrapyramidal symptoms or EPS.
Second-generation antipsychotics like risperidone, olanzapine, quetiapine, and aripiprazole block D2 less avidly than first-generation agents like haloperidol, and they add 5-HT2A serotonin receptor blockade which appears to partly protect against EPS. The trade-off is that they more often produce metabolic side effects (weight gain, dyslipidemia, diabetes) through different receptor profiles.
Hold the dichotomy. D1 in the direct pathway, D2 in the indirect pathway. Both activated by dopamine, both producing movement. Every antipsychotic perturbs this system. Every Parkinson's treatment supports it. The clinical fluency to predict how a dopaminergic drug will act starts here.