Acceleration of rat brain beta-adrenoceptor subsensitivity following the coadministration of histamine receptor antagonists with imipramine.
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.
Alhaider
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AA
Department of Medical Pharmacology College of Medicine, King Saud University, Riyadh.
Mustafa
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AA
D000818:Animals; D001921:Brain / Q000187:drug effects*; D002744:Chlorpheniramine / Q000494:pharmacology; D002927:Cimetidine / Q000494:pharmacology; D004327:Drinking Behavior / Q000187:drug effects; D004347:Drug Interactions; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D006633:Histamine Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D007099:Imipramine / Q000008:administration & dosage / Q000494:pharmacology*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011899:Ranitidine / Q000494:pharmacology; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*
D006633:Histamine Antagonists; D011943:Receptors, Adrenergic, beta; D002744:Chlorpheniramine; D002927:Cimetidine; D011899:Ranitidine; D011433:Propranolol; D007545:Isoproterenol; D007099:Imipramine