Acylation of sigma receptors by Metaphit, an isothiocyanate derivative of phencyclidine.
Pretreatment of guinea pig brain membranes with 1-[1-(3-isothiocyanatophenyl)cyclohexyl]piperidine (Metaphit) caused irreversible and differential inhibition of ligand binding to sigma (sigma) receptors. The concentration of Metaphit required to produce 50% inhibition of binding of [3H]1,3-di-o-tolylguanidine ([3H]DTG), [3H](+)-3-(3-hydroxy-phenyl)-N-(1-propyl)piperidine ([3H](+)-3-PPP), and [3H](+)-N-allylnormetazocine ([3H](+)-SKF 10,047) to sigma receptors was 2, 10 and 50 microM, respectively. This compares to a value of 10 microM for inhibition of [3H]1-[1-(2-thienyl)cyclohexyl]piperidine [( 3H]TCP) binding to phencyclidine (PCP) receptors. While Metaphit was an irreversible, non-competitive inhibitor at PCP receptors, this compound produced irreversible, competitive inhibition at sigma receptors.
Bluth
L S
LS
Division of Biology and Medicine, Brown University, Providence, RI 02912.
Rice
K C
KC
Jacobson
A E
AE
Bowen
W D
WD
D000215:Acylation; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001923:Brain Chemistry / Q000187:drug effects; D004594:Electrophysiology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D010622:Phencyclidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017981:Receptors, Neurotransmitter / Q000378:metabolism; D011957:Receptors, Opioid / Q000378:metabolism*; D017465:Receptors, Opioid, delta; D017478:Receptors, Phencyclidine
D010880:Piperidines; D017981:Receptors, Neurotransmitter; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017478:Receptors, Phencyclidine; C044705:metaphit; C026539:preclamol; D010622:Phencyclidine