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.