An opioid benzodiazepine

Although the benzodiazepines have been extensively investigated since their discovery about 20 years ago 1 , only recently have antagonists of the classical actions of benzodiazepines been described 2 . We have now discovered a class of benzodiazepines which have lost all affinity for benzodiazepine binding sites but which have moderate to high affinity for opiate receptors. Depending on the substituents introduced, it is possible to obtain compounds with selective actions on μ, δ and κ subpopulations of opiate receptors. The compounds are effective analgesics in various animal models of pain, exhibit an opioid activity spectrum in various test systems, and show none of the typical effects of minor tranquillizers. Here we report that 1-methyl-2(3-thienylcarbonyl)-aminomethyl-5-(2-fluorophenyl)- H -2,3-dihydro-l,4-benzodiazepine (KC5103; tifluadom), acts selectively on opiate κ -receptors.