Flunitrazepam binding sites in rat diaphragm. Receptors for direct neuromuscular effects of benzodiazepines?
The evidence for direct muscle relaxant effects of benzodiazepines is controversial. We now show that a crude membrane preparation of rat diaphragm possesses binding sites for [3H]flunitrazepam (FNZ). Scatchard analysis gave a binding site density of 1689 +/- 143 fmol/mg protein (Kd = 25.6 +/- 2.6 nM). These sites are of the "peripheral" type since clonazepam fails to displace [3H]FNZ as effectively as R05-4864 (IC50 values: 7.5 x 10(-6) M and 8 x 10(-9) M, respectively). Diazepam is almost as effective as R05-4864 and potently displaces [3H]FNZ binding (IC50 = 3 x 10(-8) M). We propose that the previously described effects of diazepam on rat diaphragm are mediated through high-affinity binding sites.
D000818:Animals; D014151:Anti-Anxiety Agents / Q000378:metabolism*; D001569:Benzodiazepines / Q000494:pharmacology; D001665:Binding Sites; D003964:Diaphragm / Q000378:metabolism; D005445:Flunitrazepam / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009469:Neuromuscular Junction / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D011955:Receptors, Drug / Q000032:analysis*; D011963:Receptors, GABA-A
D014151:Anti-Anxiety Agents; D011955:Receptors, Drug; D011963:Receptors, GABA-A; D001569:Benzodiazepines; D005445:Flunitrazepam