Actions of ORG 5222 as a novel psychotropic agent.

Pharmacology, Biochemistry, and Behavior
B CostallD M Tomkins

Abstract

ORG 5222 is a tetracyclic compound with high affinity for dopamine and 5-HT2 receptors. ORG 5222 was compared to fluphenazine in behavioural tests and was shown to be less potent to cause catalepsy on peripheral administration or to induce asymmetric body posturing following intrastriatal injection. On injection into the nucleus accumbens, ORG 5222 antagonised spontaneous and amphetamine-induced hyperactivity. The peripheral administration of ORG 5222 antagonised the hyperactivity induced by infusion of dopamine into the nucleus accumbens of rat or ventral striatum of the marmoset and, unlike the use of fluphenazine, there was no evidence of a 'rebound' hyperactivity after discontinuation of treatment. Furthermore, ORG 5222 prevented changes in responsiveness to dopamine agonist challenge following dopamine infusion. In a mouse black and white test box and the rat elevated plus maze ORG 5222 released exploratory behaviour suppressed by the aversive white or elevated environments. It is concluded that ORG 5222 is effective to antagonise mesolimbic dopamine function in the rodent and primate and an aversive behaviour in rodent tests. Such effects reveal a novel profile of action of ORG 5222 in behavioural paradigms predictive of ...Continue Reading

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Citations

Oct 1, 1996·Pharmacology, Biochemistry, and Behavior·T InoueT Koyama
Apr 18, 2008·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Mei HuangHerbert Y Meltzer
Nov 26, 2015·Journal of the American Academy of Child and Adolescent Psychiatry·Robert L FindlingMaju Mathews
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May 6, 2014·Expert Opinion on Drug Metabolism & Toxicology·Leslie Citrome
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Jul 21, 2010·Expert Opinion on Pharmacotherapy·Arpi Minassian, Jared W Young

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