Interaction of enantiomeric pairs of opiates with phencyclidine binding sites in rat brain: identification of (+) pentazocine as a ligand potentially suitable for imaging sigma binding sites using positron emission tomography.
Some unnatural opiates, which do not interact with classical opiate receptors, interact with phencyclidine (PCP) receptors. Among their many pharmacological actions, drugs which bind to the PCP receptor antagonize the actions of glutamic acid mediated via the NMDA excitatory amino acid receptor, leading to their potential use as anti-ischemic and anticonvulsant agents. Despite an enormous effort, identification of a PCP receptor antagonist, which would be useful for research and therapeutics, has not yet been reported. Chemical modification of unnatural opiates as a means to produce a PCP antagonist, or PCP agonists with properties different than PCP, has not been fully explored. Towards this end, we determined the equilibrium dissociation constants of eight enantiomeric pairs of opiates for the rat brain PCP receptor.
Rothman
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RB
Laboratory of Clinical Science, NIMH, Bethesda, MD 20892.
Bykov
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V
Newman
A H
AH
Jacobson
A E
AE
Rice
K C
KC
D000818:Animals; D001921:Brain / Q000378:metabolism*; D008024:Ligands; D008297:Male; D009294:Narcotics / Q000378:metabolism*; D010423:Pentazocine / Q000032:analysis*; D010622:Phencyclidine / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D011957:Receptors, Opioid / Q000378:metabolism; D017478:Receptors, Phencyclidine; D017480:Receptors, sigma; D013237:Stereoisomerism; D014055:Tomography, Emission-Computed
D008024:Ligands; D009294:Narcotics; D017981:Receptors, Neurotransmitter; D011957:Receptors, Opioid; D017478:Receptors, Phencyclidine; D017480:Receptors, sigma; D010622:Phencyclidine; D010423:Pentazocine