Doubtful role for phencyclidine metabolites in PCP enhancement of QNB binding.
In vivo administration of phencyclidine (PCP) has been shown to enhance the accumulation of intravenously administered 3H quinuclidinyl benzilate (QNB) in certain regions of mouse brain. Since this effect can be blocked by prior administration of atropine, it has been interpreted as an enhancement by PCP of the specific binding of QNB. The present studies replicated this earlier work and determined that two major hydroxy metabolites of PCP found in rodents 1-(1-phenylcyclohexyl)4-hydroxy piperidine (4-OH-pip PCP) and 1-(1-phenyl-4-hydroxycyclohexyl)piperidine (4-OH-cyclo PCP) probably do not contribute substantially to the PCP effect on QNB binding. Though QNB accumulation in brain was increased by injection of 4-OH-cyclo PCP, the doses necessary for the effect were substantially higher than those needed for PCP. Furthermore, pretreatment of the animals with beta-diethylaminoethyl diphenylpropylacetate (SKF525A), a compound known to block the metabolism of PCP in liver microsomes and thus the formation (at least in part) of these metabolites, did not attentuate the PCP effect on QNB binding.
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010622:Phencyclidine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D011335:Proadifen / Q000494:pharmacology; D011812:Quinuclidines / Q000378:metabolism*; D011813:Quinuclidinyl Benzilate / Q000378:metabolism*
D011812:Quinuclidines; C031107:4-phenyl-4-piperidinocyclohexanol; D011813:Quinuclidinyl Benzilate; C042378:1-(1-phenylcyclohexyl)-4-phenyl-4-piperidinol; D011335:Proadifen; D010622:Phencyclidine