Behavioural pharmacology of trans-5-chloro-2-methyl-2,3,3a,12b-tetrahydro- 1H-dibenz[2,3:6,7]oxepino-[4,5-c]pyrrolidine maleate, a compound interacting with dopaminergic and serotonergic receptors.

Abstract	trans-5-Chloro-2-methyl-2,3,3a,12b-tetrahydro-1H- dibenz[2,3:6,7]oxepinol[4,5-c]pyrrolidine maleate (Org 5222) is a new compound with effects on animal behaviour indicating strong antipsychotic potential based on antagonism of dopaminergic and serotonergic effects. The compound inhibits apomorphine-induced climbing behaviour, mouse locomotor activity, rat activity in an open field, shuttle box behaviour in rats, pergolide induced circling in 6-hydroxydopamine(6-OHDA) lesioned rats, serotonin agonist-induced forepaw treading, head shakes and penile erections. The compound is less effective in inducing catalepsy, and antagonising SKF-38393 (tetrahydro- 1-phenyl-1H-3-benzazepine-7,8-diol HCl)-induced circling in 6-OHDA-lesioned rats and it does not induce perioral movements in rats. Based on these data and the neurochemical profile of the compound it was decided that this compound merits clinical investigation in a programme aiming for an effective antipsychotic agent with reduced risks of extrapyramidal side-effects.
Authors	C L Broekkamp, J S De Graaf, A M van Delft
Journal	Arzneimittel-Forschung (Arzneimittelforschung) Vol. 40 Issue 5 Pg. 544-9 (May 1990) ISSN: 0004-4172 [Print] Germany
PMID	1974432 (Publication Type: Comparative Study, Journal Article)
Chemical References	Antipsychotic Agents Dibenzocycloheptenes Dibenzoxepins Heterocyclic Compounds, 4 or More Rings Receptors, Dopamine Receptors, Serotonin Clozapine Haloperidol asenapine Chlorpromazine
Topics	Animals Antipsychotic Agents (pharmacology) Avoidance Learning (drug effects) Behavior, Animal (drug effects) Catalepsy (chemically induced) Chlorpromazine (pharmacology) Clozapine (pharmacology) Conflict, Psychological Dibenzocycloheptenes Dibenzoxepins (pharmacology) Haloperidol (pharmacology) Heterocyclic Compounds, 4 or More Rings Male Mice Mice, Inbred ICR Motor Activity (drug effects) Rats Rats, Inbred Strains Receptors, Dopamine (drug effects) Receptors, Serotonin (drug effects) Stereotyped Behavior (drug effects)

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