Uncompetitive inhibition of [3H]1,3-di-o-tolyl-guanidine-defined sigma binding sites by desipramine, propranolol and alprenolol in rat brain.
Desipramine, imipramine, clomipramine, (-)-propranolol, (-)-alprenolol, (+/-)-pentazocine and risperidone caused a concentration-dependent inhibition of 6 nM [3H]DTG (1,3-di-o-tolylguanidine)-defined sigma (sigma) binding with Ki values of about 0.5-2.5 microM in well-washed homogenates obtained from rat cerebral cortex. The saturation studies revealed that the inhibition by desipramine (1-4 microM), (-)-propranolol (1 microM) and (-)-alprenolol (3 microM) resulted from a reduction of the Bmax value without alteration of the Kd of [3H]DTG binding to the cortex or hippocampus. In contrast, imipramine, (+/-)-pentazocine, clomipramine and risperidone competitively attenuated the cortical or hippocampal [3H]DTG binding. These findings demonstrate the uncompetitive inhibition of [3H]DTG binding by neuroactive drugs, thereby providing further support for the possible multiple regulation of cerebral sigma receptors.
Shirayama
Y
Y
Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
Takahashi
K
K
Nishikawa
T
T
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000526:Alprenolol / Q000494:pharmacology*; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D003891:Desipramine / Q000494:pharmacology*; D006146:Guanidines / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D011433:Propranolol / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017480:Receptors, sigma / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000319:Adrenergic beta-Antagonists; D000929:Antidepressive Agents, Tricyclic; D006146:Guanidines; D017480:Receptors, sigma; D000526:Alprenolol; D011433:Propranolol; C050232:1,3-ditolylguanidine; D003891:Desipramine