Changes in the sensitivity of the central alpha- and beta-adrenergic systems during desmethylimipramine treatment as assessed by plasma growth hormone response in the baboon.
The tricyclic antidepressant desmethylimipramine (DMI) 2.5 mg/kg IM was administered to adolescent baboons once daily for 21 days, to investigate changes in alpha- and beta-noradrenergic function. Prior to DMI treatment, plasma growth hormone (GH) responses to the intravenous infusion of an alpha 2-adrenergic receptor agonist, clonidine, or a beta 2-adrenergic antagonist, ICI 118,551, were determined. DMI, 2.5 mg/kg, administered acutely did not stimulate the release of GH (up to 4 h post injection). The GH response to clonidine was decreased 4 h after DMI, 2.5 mg/kg. Alterations in plasma GH response to clonidine and ICI 118,551 were evident during and after chronic DMI administration. The GH response to clonidine was significantly diminished after 2 days, and gradually returned to the pretreatment amplitude over 7-21 days of treatment, with an overshoot 2 days after DMI withdrawal. After 21 days of DMI administration the GH response to ICI 118,551 was significantly enhanced, and remained consistently elevated during a withdrawal period of 21 days. These changes in the response to an alpha-adrenergic agonist and a beta-adrenergic antagonist indicate that the long term regulatory changes in receptor sensitivity, occurring between 2 and 21 days of DMI treatment, compensate for the acute effects of DMI on these responses.
D000818:Animals; D001921:Brain / Q000187:drug effects*; D003000:Clonidine / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology*; D005260:Female; D013006:Growth Hormone / Q000097:blood*; D006801:Humans; D008297:Male; D010215:Papio; D011412:Propanolamines / Q000494:pharmacology; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D013375:Substance Withdrawal Syndrome / Q000097:blood
D011412:Propanolamines; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; C026777:ICI 118551; D013006:Growth Hormone; D003000:Clonidine; D003891:Desipramine