PHARMACOLOGICAL CHARACTERIZATION OF BUPRENORPHINE, A MIXED AGONIST-ANTAGONIST WITH KAPPA(3) ANALGESIA

Buprenorphine is a mixed opioid agonist/antagonist analgesic. This stu dy was designed to determine the role of opioid receptor subtypes, esp ecially kappa(3), in buprenorphine-induced analgesia in mice. Buprenor phine, when injected systemically, revealed a potent analgesic effect by taiIflick assay, with a biphasic dose-response curve, which was rev ersed by naloxone. The presence of analgesic cross-tolerance between b uprenorphine and naloxone benzoylhydrazone (NalBzoH) and morphine indi cated a role for kappa(3) and mu receptor subtype in buprenorphine ana lgesia. Additional studies with selective opioid antagonists indicated kappa(1) mechanisms of action. We did not detect any involvement of t he delta receptor subtype. Low doses of buprenorphine antagonized morp hine analgesia, while high doses of buprenorphine coadministered with morphine elicited increasing analgesia in a dose-dependent manner. The se findings suggest that buprenorphine elicits analgesia through an in teraction with kappa(3) receptors and to a lesser extent with kappa(1) as well as its activity as partial mu receptor agonist.