Interactions of erythro-ifenprodil, threo-ifenprodil, erythro-iodoifenprodil, and eliprodil with subtypes of sigma receptors.
Observations of sigma (sigma) receptor heterogeneity have prompted interest in identifying ligands for sigma receptor subtypes. Selective ligands for the sigma-2 are unavailable, but [3H]ifenprodil labels sigma-2 sites. Therefore, isomers and analogues of ifenprodil were compared as potential sigma-2 ligands. Threo-ifenprodil and erythro-ifenprodil had high affinity (Ki congruent to 2 nM) for sigma-2 sites; erythro-iodoifenprodil had moderate affinity (Ki congruent to 46 nM); eliprodil had lowest affinity (Ki congruent to 630 nM). Threo-ifenprodil, which has less affinity for alpha 1-adrenoceptors than erythro-ifenprodil, was slightly more selective than erythro-ifenprodil for sigma-2 sites. These results identify threo-ifenprodil as potentially useful for studies of sigma-2 receptors.
Hashimoto
K
K
Neuroimaging and Drug Action Section, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA.
London
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ED
D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D004347:Drug Interactions; D066298:In Vitro Techniques; D007700:Kinetics; D008024:Ligands; D008297:Male; D010423:Pentazocine / Q000378:metabolism; D010880:Piperidines / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D017480:Receptors, sigma / Q000187:drug effects* / Q000378:metabolism; D013237:Stereoisomerism
D008024:Ligands; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; D017480:Receptors, sigma; C093453:iodoifenprodil; C010739:ifenprodil; D010423:Pentazocine; C058083:eliprodil