title: Biochemical effects in rats after acute and long-term treatment with clovoxamine.
abstract: Clovoxamine, a nontricyclic antidepressant, has a dual action in blocking the reuptake of both noradrenaline and serotonin. Acute in vitro receptor binding studies showed that clovoxamine has little affinity for muscarinic, histaminergic, serotonergic and adrenergic binding sites. After chronic administration, clovoxamine induced a decrease in the functional beta-adrenergic receptor coupled c-AMP response. A comparison made between clovoxamine (with a very short half life value in rats) and desipramine indicated that the decrease in the beta-receptor coupled c-AMP response was similar, regardless whether the compounds were injected i.p. twice daily (10 mg/kg) or delivered via an osmotic minipump (20 mg/kg/day) for 21 days. Chronic administration of both clovoxamine and desipramine by twice daily i.p. injections or osmotic minipumps in rats resulted also in a down regulation of the number of 5-HT2 receptors in frontal cortex. The alteration in beta-receptor number (Bmax) did not correlate with the decrease in adenylate cyclase activity. These data support a multistep process of the down regulation of the beta-adrenergic system in which the first step is the uncoupling of the receptors resulting in a decrease in the agonist-stimulated adenylate cyclase without necessarily a change in Bmax. The observed biochemical effects in rats after acute and chronic administration with clovoxamine further support the antidepressant activity of this compound.
authors.forename: L D
authors.initials: LD
authors.lastname: Bradford
authors.forename: M T
authors.initials: MT
authors.lastname: Tulp
authors.forename: J
authors.initials: J
authors.lastname: Schipper
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001923:Brain Chemistry / Q000187:drug effects*; D000242:Cyclic AMP / Q000378:metabolism; D003891:Desipramine / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D010091:Oximes / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D011985:Receptors, Serotonin / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D013574:Synaptosomes / Q000378:metabolism; D013997:Time Factors
chemical_list: D000928:Antidepressive Agents; D010091:Oximes; D011943:Receptors, Adrenergic, beta; D011985:Receptors, Serotonin; D012701:Serotonin; C020724:clovoxamine; D000242:Cyclic AMP; D003891:Desipramine; D009638:Norepinephrine