Acceleration of rat brain beta-adrenoceptor subsensitivity following the coadministration of histamine receptor antagonists with imipramine

Abstract

Systemic administration of isoprenaline to rats produced a dose-dependent increase in water drinking which was effectively blocked by propranolol. This dipsogenic effect was significantly inhibited by the subacute (4 days) administration of imipramine (18.1 mg/kg/day) together with either the H1-histamine receptor antagonist, chlorpheniramine (0.1 or 1.32 mg/kg/day), or the H2-histamine antagonist, cimetidine (1.91 mg/kg/day) or ranitidine (0.60 or 1.51 mg/kg/day). The oral subacute administration of imipramine alone had no significant effect on this behavior. However, chronic ingestion of imipramine alone (21 days) caused a significant reduction in the isoprenaline-induced behavior. It is concluded that the desensitization of central beta-adrenoceptors, as evidenced by inhibition of isoprenaline-induced drinking, can be accelerated following the oral subacute co-administration of imipramine with either H1- or H2-histamine receptor antagonists. It is also seems the central histamine receptors may partially contribute towards the mechanism of antidepressant effect of imipramine.

Dose‐Dependent Inhibition of the CYP2D6 Catalyzed Oxidation of Sparteine by Mepyramine in Healthy Volunteers

“…This is somewhat surprising with chlorpheniramine because it is metabolized by this CYP enzyme (Yasuda et al 1995). The coadministration of chlorpheniramine and imipramine enhances the effect of imipramine in the rat (Alhaide & Mustafa 1989), suggesting that chlorpheniramine may inhibit metabolism of imipramine by CYP2D6. In fact, Hamelin et al (1998) recently reported that the K i values of chlorpheniramine and clemastine were ∂11 and ∂2 mM, respectively.…”