ISOCLOZAPINE is typical antipsychotic that acts by blocking the receptors in the brain’s dopamine pathways. Isoclozapine has high affinities at both DA (D1 and D2) and serotonin (5-HT2A and 5-HT2C) receptors. Isoclozapine shows the greatest antipsychotic potential on inhibition of apomorphine-induced climbing in mice at quite low doses under sc or po administrations. However, Isoclozapine also produces catalepsy at low doses.

(S)-SKF-83959 (MCL 201) is enantiomer of D1 receptor agonist SKF-83959. (S)-SKF-83959 is reported to be a functionally selective dopamine D1 receptor ligand with much lower affinity to dopamine D2, D3 and D5 receptors. (R)-SKF-83959 like SKF-83959, produced dose related effects on overt behavior (eye blinking) and schedule-controlled performance in squirrel monkeys. (R)-SKF-83959 increases in eye blinking and decreases in rates of fixed-ratio responding. In contrast to the effects of its S-(-) enantiomer, was relatively devoid of behavioral activity up to doses that were approximately 10-fold greater than (R)-SKF-83959.

P-88-8991 (Hydroxy Iloperidone, 4-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl] propoxy]- 3-methoxy-methylbenzenemethanol) is the major active metabolite of Iloperidone an atypical antipsychotic that used for the acute treatment of schizophrenia in adults. Metabolic reduction of Iloperidone carbonyl group leads to P-88-8991 in rats, dogs, and humans. The receptor affinity profile of P-88-8991 is comparable to that of iloperidone: this metabolite binds to the serotonin 5-HT2A receptors, adrenergic alpha1 and alpha2C receptors, and D2A receptors and with lower affinity to other monoamine (dopamine, serotonin, and histamine H1 ) receptors. The comparable receptor binding profile of P-88-8991 indicates that it is likely to contribute to the clinical profile of iloperidone. Preclinical experiments, such as the mouse apomorphine climbing test, the rat self-stimulation, and the pole climb avoidance task, indicate antipsychotic activity of P88-8991 and confirm that this metabolite crosses the blood–brain barrier