PT  - JOURNAL ARTICLE
AU  - M R Szewczak
AU  - R Corbett
AU  - D K Rush
AU  - C A Wilmot
AU  - P G Conway
AU  - J T Strupczewski
AU  - M Cornfeldt
TI  - The pharmacological profile of iloperidone, a novel atypical antipsychotic agent.
DP  - 1995 Sep 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 1404--1413
VI  - 274
IP  - 3
4099  - http://jpet.aspetjournals.org/content/274/3/1404.short
4100  - http://jpet.aspetjournals.org/content/274/3/1404.full
SO  - J Pharmacol Exp Ther1995 Sep 01; 274
AB  - Iloperidone (1-[4-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1- piperidinyl]propoxy]-3-methoxyphenyl]ethanone) demonstrated a potent antipsychotic profile in several in vitro and in vivo animal models. Iloperidone displaced ligand binding at D2 dopamine receptors (IC50 = 0.11 microM) and displayed a high affinity for serotonin (5-HT2) receptors (IC50 = 0.011 microM) and alpha-1 receptors (IC50 = 0.00037 microM). In vivo, iloperidone antagonized apomorphine-induced climbing behavior in mice at low doses with good oral bioavailability, prevented 5-HT-induced head twitch in rats at low doses, and inhibited self-stimulation behavior in rats, pole climb avoidance in rats and continuous Sidman avoidance responding in monkeys. The latter assay also demonstrated a good duration of action. Iloperidone was substantially less active in models of extrapyramidal side effect (EPS) liability, such as preventing apomorphine-induced stereotypy and causing catalepsy in rats. In single dopamine neuron sampling studies, iloperidone demonstrated clozapine-like effects on the number of active midbrain dopamine neurons. Based on the significant increase in the open arm time seen after iloperidone treatment in the elevated plus maze assay and increased interaction score in social interaction, iloperidone may also have favorable effects in the clinic on anxiety and, possibly, negative symptoms. Clinical trials are under way of the use of iloperidone for the treatment of schizophrenia.