Abstract |
The atypical antipsychotic drug clozapine interacts with multiple transmitter systems, among them the D4 subtype of dopamine receptors. PNU-96415E is chemically unrelated to clozapine and has its highest binding affinity for the D4 and 5-HT2A receptors. In comparison to clozapine, PNU-96415E is weaker in binding to D1, D2, alpha1 and muscarinic receptors. PNU-96415E inhibited exploratory locomotor activity in mice and rats, and antagonized d-amphetamine-induced locomotor stimulation in rats. It antagonized apomorphine-induced cage climbing, and blocked head and body twitch produced by 5-HTP in mice. Like clozapine, but unlike haloperidol, PNU-96415E did not antagonize stereotypic behaviors produced by a high dose of d-amphetamine or methylphenidate in rats and mice. PNU-96415E blocked conditioned avoidance in rats but produced no catalepsy, a pattern similar to clozapine but different from haloperidol. In rats trained to discriminate clozapine from saline injections, the stimulus effect generalized completely with PNU-96415E, but not haloperidol. This profile of pharmacological activities is consistent with that of an atypical antipsychotic and, as in the case with clozapine, the behavioral effects of PNU-96415E cannot be ascribed to a single receptor mechanism.
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Authors | A H Tang, S R Franklin, C S Himes, M W Smith, R E Tenbrink |
Journal | The Journal of pharmacology and experimental therapeutics
(J Pharmacol Exp Ther)
Vol. 281
Issue 1
Pg. 440-7
(Apr 1997)
ISSN: 0022-3565 [Print] United States |
PMID | 9103528
(Publication Type: Journal Article)
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Chemical References |
- Antipsychotic Agents
- PNU 96415E
- Piperazines
- Receptors, Dopamine
- Receptors, Serotonin
- Clozapine
- Dextroamphetamine
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Topics |
- Animals
- Antipsychotic Agents
(pharmacology)
- Avoidance Learning
(drug effects)
- Clozapine
(pharmacology)
- Dextroamphetamine
(pharmacology)
- Dose-Response Relationship, Drug
- Male
- Mice
- Motor Activity
(drug effects)
- Piperazines
(pharmacology)
- Rats
- Rats, Inbred F344
- Rats, Sprague-Dawley
- Receptors, Dopamine
(metabolism)
- Receptors, Serotonin
(metabolism)
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