The ratios of serotonin₂ and dopamine₂ affinities differentiate atypical and typical antipsychotic drugs

Atypical antipsychotic drugs such as clozapine, fluperlapine, and melperone produce weak catalepsy in rodents, and minimal extrapyramidal symptoms and serum prolactin elevations in humans, compared to typical antipsychotic drugs such as haloperidol. The biological basis for these differences has been attributed to relatively weak blockade at D₂ dopamine (DA) receptors, various effects at D₁ receptors, or potent serotonin₂ (5-HT₂) antagonism, although other possibilities exist. To clarify the relative importance of actions at D₁, D₂, and 5-HT₂ receptors for identification of candidate typical and atypical drugs, we determined the negative log of the Ki (pKi) value of 21 typical and 17 atypical antipsychotic drugs for the striatal D₁ and D₂ and frontal cortex 5-HT₂ receptors of rodent brain. Cluster analysis identified that the 5-HT₂/D₂ ratio was the most successful means of utilizing this data to classify typical and atypical antipsychotic drugs correctly. A 92 percent accuracy was achieved.