Dose-dependent down-regulation of beta-adrenergic receptors after chronic intravenous infusion of antidepressants.
1. The effects of intravenous infusion of desipramine (1, 3, 10, and 60 mg/kg/day), amitriptyline, zimelidine, iprindole (3, 10, 30, 60, and 100 mg/kg/day each), imipramine (10, 30, and 100 mg/kg/day), or U-48753E (1, 3, 10, and 30 mg/kg/day) on the density of central beta-adrenergic receptors (beta-AR) were investigated in female Sprague-Dawley rats. 2. Desipramine, amitriptyline, zimelidine, iprindole, imipramine, and U-48753E dose-dependently reduced the density of beta-AR in the cerebral cortex. 3. The time of onset of down-regulation of beta-AR was negatively correlated with the doses of drugs. 4. At equipotent doses, antidepressants seem to have a similar profile for the time of onset of reduction in the density of beta-AR. 5. The results indicate that down-regulation of beta-AR may be involved in mediating the therapeutic effects of antidepressants, and this effect can be rapidly achieved by intravenous infusion of drugs.
Sethy
V H
VH
CNS Diseases Research and Biostatistics, Upjohn Company, Kalamazoo, MI.
Day
J S
JS
Cooper
M M
MM
D000639:Amitriptyline / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000378:metabolism*; D003517:Cyclopentanes / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D007099:Imipramine / Q000494:pharmacology; D007262:Infusions, Intravenous; D007488:Iprindole / Q000494:pharmacology; D007700:Kinetics; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*; D012016:Reference Values; D015031:Zimeldine / Q000494:pharmacology
D000928:Antidepressive Agents; D003517:Cyclopentanes; D011943:Receptors, Adrenergic, beta; D000639:Amitriptyline; D015031:Zimeldine; C033295:U 78753E; D007488:Iprindole; D007099:Imipramine; D003891:Desipramine