n-cyclopropylmethylnorazidomorphine and thiobutabarbital

In order to analyse opiate receptors mediating anti-nociception, the activity pattern of different opiates was determined by using hot-plate (45 degrees C and 56 degrees C), tail-flick and algolytic tests on rats, and the acetic acid stretching test on mice, for evaluation of analgesic activity. Potentiation of barbiturate anaesthesia, measurement of pupillary diameter, and a modification of pentetrazol convulsion, were used for evaluation of non-analgesic activity. The efficacy and affinity constant (pA2) of the proposed opiate A receptor agonist and B receptor antagonist drug N-cyclopropylmethyl-norazido-dihydroisomorphine (CAM) were determined. CAM produced several opiate agonist (morphine-like) effects, often stronger than morphine, in three of the analgesic tests and two of the non-analgesic tests. On the other hand CAM proved to be a very strong narcotic antagonist, as potent as naloxone as evidenced by identical pA2 values, in the algolytic, 45 degrees C hot-plate and pentetrazol tests, but not in the 56 degrees C hot-plate, tail-flick and acetic acid tests. The potency differences for the actions of morphine and CAM in a heat test (56 degrees C hot-plate) compared with a non-heat test (acetic acid stretching) were found to be 8.6 and 540 respectively. It is concluded that opiate analgesia might be mediated by at least two receptors classified in terms of the antagonistic or agonistic activity of CAM.

Topics: Analgesics, Opioid; Animals; Dose-Response Relationship, Drug; Female; Lethal Dose 50; Male; Mice; Morphinans; Morphine; Nalorphine; Narcotic Antagonists; Oxymorphone; Pentazocine; Rats; Receptors, Opioid; Thiopental