Effect of paroxetine, a selective 5-hydroxytryptamine uptake inhibitor, on beta-adrenoceptors in rat brain: autoradiographic and functional studies.
Quantitative receptor autoradiography was used to investigate the effects of paroxetine (8.3 mg/kg), amitriptyline (26 mg/kg) and desipramine (17 mg/kg), administered daily in the drinking water for 21 days, on the number of beta 1- and beta 2-adrenoceptors in the cortex of the rat. In addition, the effect of these drugs on the function of beta-adrenoceptors was examined by measuring noradrenaline- and isoprenaline-stimulated production of cyclic AMP in slices of cortex. Paroxetine did not alter the number of cortical beta 1 or beta 2-adrenoceptors nor did it induce any functional changes in beta-adrenoceptor-linked adenylyl cyclase. In contrast, desipramine caused a significant reduction in the density of beta 1-adrenoceptors and in the sensitivity of both noradrenaline and isoprenaline-stimulated adenylyl cyclase. Although amitriptyline significantly reduced the number of beta 1-adrenoceptors in cortical membranes, no such changes could be detected by autoradiography. It is apparent from these and other studies, that the ability of antidepressants to down-regulate central beta-adrenoceptors is not a property shared by all antidepressants. In particular, the more potent and selective inhibitors of the uptake of 5-HT, such as paroxetine, appear to be devoid of effects on this receptor system.
SmithKline Beecham Pharmaceuticals, Research and Development, Harlow, Essex.
D R
DR
Nelson
G D
GD
Pratt
K J
KJ
Palmer
A M
AM
Johnson
N G
NG
Bowery
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000639:Amitriptyline / Q000494:pharmacology; D000818:Animals; D001345:Autoradiography; D001923:Brain Chemistry / Q000187:drug effects*; D000242:Cyclic AMP / Q000378:metabolism; D003891:Desipramine / Q000494:pharmacology; D007457:Iodine Radioisotopes; D020120:Iodocyanopindolol; D007700:Kinetics; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D017374:Paroxetine; D010869:Pindolol / Q000031:analogs & derivatives; D010880:Piperidines / Q000494:pharmacology*; D011412:Propanolamines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000494:pharmacology*
D000319:Adrenergic beta-Antagonists; D007457:Iodine Radioisotopes; D010880:Piperidines; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D012702:Serotonin Antagonists; D000639:Amitriptyline; D017374:Paroxetine; D020120:Iodocyanopindolol; D010869:Pindolol; D000242:Cyclic AMP; C033394:CGP 12177; D003891:Desipramine