Why is amitriptyline much weaker than desipramine at decreasing beta-adrenoceptor numbers?
Desipramine is consistently more effective than amitriptyline at causing beta-adrenoceptor down-regulation. Atropine, mepyramine, ketanserin, cyproheptadine and citalopram did not modify this action of desipramine in rats. Therefore inhibition of either muscarinic, histamine-H1, and 5-HT receptors or 5-HT uptake produced by amitriptyline is unlikely to account for its weaker effect on beta-adrenoceptors. A more likely explanation implicates noradrenaline uptake inhibition in vivo since amitriptyline was much weaker than desipramine and only effective after repeated dosing.
Wise
H
H
Halliday
C A
CA
D000639:Amitriptyline / Q000494:pharmacology*; D000818:Animals; D003891:Desipramine / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D009661:Nortriptyline / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000032:analysis / Q000187:drug effects*
D011943:Receptors, Adrenergic, beta; D000639:Amitriptyline; D009661:Nortriptyline; D003891:Desipramine; D009638:Norepinephrine