1,3-Di(2-[5-3H]tolyl)guanidine labels more than one site in rat forebrain.
Studies of 1,3-di-(2-[5-3H]tolyl)guanidine ([3H]DTG) binding to rat brain membranes revealed that [3H]DTG binds to a high and a low affinity site with Kd values of 19.8 nM and 1.31 microM (corresponding Bmax values 291 fmol/mg protein and 8.68 pmol/mg protein). The order of potency of competitors for [3H]DTG binding revealed a binding profile typical of sigma site ligands. Several sigma ligands such as the enantiomers of 3-PPP (3-(3-hydroxyphenyl)-N- (n-propyl)piperidine) and (+/-)-pentazocine exhibited biphasic competition profiles for [3H]DTG binding, whereas other sigma ligands such as haloperidol displayed monotonic competition curves. Neither phenytoin nor carbamazepine were observed to enhance [3H]DTG binding. These data support the hypothesis that multiple sigma binding sites exist. The lack of phenytoin and carbamazepine modulation of [3H]DTG binding are in agreement with the proposed greater density of sigma site 2 in the rat, since allosteric modulation has been ascribed to the DM1/sigma 1 site.
Codd
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Drug Discovery Research, R.W. Johnson Pharmaceutical Research Institute, Spring House, PA 19477-0776.
Shank
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RP
D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D002220:Carbamazepine / Q000494:pharmacology; D006146:Guanidines / Q000378:metabolism*; D006220:Haloperidol / Q000378:metabolism; D008297:Male; D010423:Pentazocine / Q000378:metabolism*; D010672:Phenytoin / Q000494:pharmacology; D010880:Piperidines / Q000378:metabolism*; D016548:Prosencephalon / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017480:Receptors, sigma / Q000378:metabolism; D013237:Stereoisomerism
D006146:Guanidines; D010880:Piperidines; D017480:Receptors, sigma; D002220:Carbamazepine; D010672:Phenytoin; C026539:preclamol; D006220:Haloperidol; C050232:1,3-ditolylguanidine; D010423:Pentazocine