TY - JOUR
T1 - Kappa3 receptors and levorphanol-induced analgesia
AU - Tive, L.
AU - Ginsberg, K.
AU - Pick, C. G.
AU - Pasternak, G. W.
PY - 1992/9
Y1 - 1992/9
N2 - Levorphanol is a widely used opiate analgesic. Although structurally related to morphine, levorphanol has high affinity for a number of receptor subtypes, including both kappa1, and kappa3. Prior reports had implicated a kappa component of levorphanol-induced antinociception. Evidence is now presented suggesting that levorphanol-induced analgesia is produced by a mixture of mu and kappa3 mechanisms. Levorphanol was a potent analgesic in the tail-flick assay, when given systemically, spinally or supraspinally. Isobolographic analysis of the combined administration of levorphanol, spinally and supraspinally implied synergistic interactions. Naloxonazine reduced levorphanol-induced analgesia, implicating a role for mu1 receptors. The kappa1 antagonist nor-binaltorphimine at a dose which reversed analgesia induced by U50,488H did not antagonize levorphanol-induced analgesia. Additional studies revealed no cross tolerance in either direction, between levorphanol with the kappa1 analgesic U50,488H. Together, these results strongly argue against a role for kappa1, receptors in levorphanol-induced analgesia. However, mice tolerant to the kappa3 analgesic, naloxone benzoylhydrazone (NalBzoH), showed cross tolerance to levorphanol, implying a role of kappa3 mechanisms in levorphanol-induced analgesia.
AB - Levorphanol is a widely used opiate analgesic. Although structurally related to morphine, levorphanol has high affinity for a number of receptor subtypes, including both kappa1, and kappa3. Prior reports had implicated a kappa component of levorphanol-induced antinociception. Evidence is now presented suggesting that levorphanol-induced analgesia is produced by a mixture of mu and kappa3 mechanisms. Levorphanol was a potent analgesic in the tail-flick assay, when given systemically, spinally or supraspinally. Isobolographic analysis of the combined administration of levorphanol, spinally and supraspinally implied synergistic interactions. Naloxonazine reduced levorphanol-induced analgesia, implicating a role for mu1 receptors. The kappa1 antagonist nor-binaltorphimine at a dose which reversed analgesia induced by U50,488H did not antagonize levorphanol-induced analgesia. Additional studies revealed no cross tolerance in either direction, between levorphanol with the kappa1 analgesic U50,488H. Together, these results strongly argue against a role for kappa1, receptors in levorphanol-induced analgesia. However, mice tolerant to the kappa3 analgesic, naloxone benzoylhydrazone (NalBzoH), showed cross tolerance to levorphanol, implying a role of kappa3 mechanisms in levorphanol-induced analgesia.
KW - analgesia
KW - kappa receptors
KW - morphine
KW - pain
UR - http://www.scopus.com/inward/record.url?scp=0026783524&partnerID=8YFLogxK
U2 - 10.1016/0028-3908(92)90121-5
DO - 10.1016/0028-3908(92)90121-5
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AN - SCOPUS:0026783524
SN - 0028-3908
VL - 31
SP - 851
EP - 856
JO - Neuropharmacology
JF - Neuropharmacology
IS - 9
ER -