Interactions between pentazocine and tripelennamine on autonomic and nociceptive measures in the dog.
Pentazocine and tripelennamine, which have been abused in combination by humans, were evaluated for pharmacologic interactions on autonomic, behavioral, and antinociceptive measures in chronic spinal dogs. Pentazocine (0.31-5 mg/kg, IV) produced miosis, hypothermia and antinociception which was mediated by spinal and supraspinal reflexes; these effects were antagonized by naltrexone. Tripelennamine (0.63-2.5 mg/kg, IV) elicited mydriasis, hyperthermia and antinociception; these effects were not blocked by naltrexone. Tripelennamine produced antinociception only on the supraspinally-mediated skin twitch reflex. Interactions between pentazocine and tripelennamine varied depending on the response measured. Effects of both drugs on pupils were additive. Temperature effects were infra-additive, with the hyperthermic effects of tripelennamine predominating over the pentazocine hypothermia, resulting in a complete physiologic antagonism of pentazocine hypothermia. Antinociception, measured by flexor reflex depression, represented only the effect of pentazocine, whereas skin twitch reflex antinociception reflected either infra-additive or additive properties. The coadministration of nonconvulsive doses of pentazocine and tripelennamine produced seizures indicating a potentiated adverse interaction. In summary, the patterns of the pentazocine-triplennamine interactions were complex and the effects of tripelennamine could not be attributed to opioid activity.
Neuropharmacology Laboratory, National Institute on Drug Abuse Addiction Research Center, Baltimore, MD 21224.
D B
DB
Vaupel
D000818:Animals; D001341:Autonomic Nervous System / Q000187:drug effects*; D001522:Behavior, Animal / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D009271:Naltrexone / Q000494:pharmacology; D009619:Nociceptors / Q000187:drug effects*; D010423:Pentazocine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011680:Pupil / Q000187:drug effects; D012018:Reflex / Q000187:drug effects; D013997:Time Factors; D014309:Tripelennamine / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D014309:Tripelennamine; D009271:Naltrexone; D010423:Pentazocine