(-)-Pentazocine analgesia in mice: interactions with a sigma receptor system.
(-)-Pentazocine is active in the tailflick assay in CD-1 mice, although it shows a biphasic dose-response curve with a peak effect of only 30%. Co-administration of haloperidol shifts the dose-response curve to the left and elevates the maximal response to 70% through a blockade of sigma 1 receptors, but the curve remains biphasic. (+)-Pentazocine is inactive in all antinociceptive assays, either alone or with haloperidol. The analgesic actions of (-)-pentazocine are readily reversed by nor-binaltorphimine, but not by the mu-selective opioid receptor antagonist beta-funaltrexamine, implying a kappa 1-opioid receptor mechanism of action. This conclusion is supported by the ability of antisense oligodeoxynucleotides directed against the KOR-1 clone, which encodes the kappa 1-opioid receptor, to block (-)-pentazocine analgesia.
Chien
C C
CC
Department of Neurology and Neuroscience, Cornell II Medical College, New York, NY 10021, USA.
Pasternak
G W
GW
D000701:Analgesics, Opioid / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D001483:Base Sequence; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D051379:Mice; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010423:Pentazocine / Q000493:pharmacokinetics / Q000494:pharmacology*; D011930:Reaction Time / Q000187:drug effects; D017465:Receptors, Opioid, delta / Q000187:drug effects / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000187:drug effects / Q000378:metabolism; D017480:Receptors, sigma / Q000187:drug effects* / Q000378:metabolism
D000701:Analgesics, Opioid; D018492:Dopamine Antagonists; D016376:Oligonucleotides, Antisense; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D017480:Receptors, sigma; D006220:Haloperidol; D010423:Pentazocine