Effect of prolonged 5-hydroxytryptamine uptake inhibition by paroxetine on cortical beta 1 and beta 2-adrenoceptors in rat brain.
The effects of prolonged (21 day) oral administration of the antidepressants paroxetine (0.9 to 8.9 mg/kg/day) and amitriptyline (2.7 to 27 mg/kg/day), on rat brain cortical beta 1- and beta 2-adrenoceptor numbers and affinities were investigated using [3H]-CGP 12177. Although amitriptyline, 27 mg/kg, caused a significant (p less than 0.05) 20% reduction in the number of beta 1-adrenoceptors, paroxetine, at doses up to 8.9 mg/kg p.o., did not influence binding of [3H]-CGP 12177 to cortical beta 1- or beta 2-adrenoceptors. This study with paroxetine provides further evidence that the down-regulation of central beta 1-adrenoceptors in rat brain after repeated administration is not a property of all antidepressant drugs.
Nelson
D R
DR
SmithKline Beecham Pharmaceuticals, Research and Development, Harlow, Essex, UK.
Palmer
K J
KJ
Johnson
A M
AM
D000319:Adrenergic beta-Antagonists; D000639:Amitriptyline / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D007093:Imidazoles; D007700:Kinetics; D008297:Male; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology*; D017374:Paroxetine; D010880:Piperidines / Q000494:pharmacology*; D011412:Propanolamines; D011869:Radioligand Assay; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000145:classification / Q000187:drug effects*; D011985:Receptors, Serotonin / Q000187:drug effects; D012701:Serotonin / Q000502:physiology*
D000319:Adrenergic beta-Antagonists; D000928:Antidepressive Agents; D007093:Imidazoles; D014179:Neurotransmitter Uptake Inhibitors; D010880:Piperidines; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D011985:Receptors, Serotonin; D000639:Amitriptyline; D012701:Serotonin; D017374:Paroxetine; C049763:CGP 20712A; C033394:CGP 12177