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The occurrence of unidirectional noncross-tolerance to heroin and etorphine induced antinociception in morphine tolerant mice prompted this study to determine whether this phenomenon occurs for opiate induced inhibition of intestinal transit. Tolerance to the intestinal inhibitory effect (charcoal meal test) of s.c. morphine, etorphine and heroin was reflected by an increase in the ED50 value and in most cases, a flattening of the dose response curve in morphine and etorphine pelleted mice (tested with pellet in place). A similar response was noted following intracerebroventricular administration of these agents in morphine pelleted mice. More tolerance developed to the relatively hydrophilic compound morphine than to the lipophilic compounds etorphine and heroin. Factors related to hydrophilicity and lipophilicity may be involved in the development of tolerance to opiates in the intestine although unidirectional non cross-tolerance did not occur.

The effects of etorphine, a potent opiate agonist without preferential affinity for mu, delta or kappa receptors, on exocrine pancreatic secretion were studied in rats fitted with chronic or acute pancreatic fistulas and compared to those of methadone, a well-documented mu agonist. In conscious rats etorphine (3 micrograms/kg s.c.) inhibited basal pancreatic secretion by about 50% for volume and bicarbonate output and by 70% for protein output. Pancreatic secretion returned to its basal level within 2 h. Methadone (5 mg/kg s.c.) was about equipotent but the inhibition lasted longer. The effects of both etorphine and methadone were completely antagonized by naloxone (1 mg/kg s.c.) and to a lesser extent by diprenorphine (10 microgram/kg s.c.). Yohimbine did not suppress the inhibitory effect of etorphine on protein output but showed some antagonism against the effects of etorphine on water and bicarbonate output. In anaesthetized rats etorphine (3 micrograms/kg) inhibited the pancreatic secretion stimulated by 2-deoxy glucose, a centrally acting vagal stimulatory agent, by 50-60% for volume and bicarbonate output and totally for protein output. The same dose of etorphine did not inhibit the pancreatic secretion evoked by vagal electrical stimulation, a peripheral stimulus. Methadone (5 mg/kg) inhibited the pancreatic secretion stimulated by 2-deoxy glucose to the same extent, but for a longer time than etorphine, and at the same dose did not suppress the pancreatic pancreatic response to vagal electrical stimulation. The inhibitory effects of etorphine and methadone in anaesthetized rats were completely suppressed by naloxone (1 mg/kg s.c.) and only reduced by diprenorphine (10 micrograms/kg s.c.).(ABSTRACT TRUNCATED AT 250 WORDS)

The capture, by means of chemical immobilization, of about 100 large African animals of 17 different species was accomplished by use of compound M.99, an oripavine with morphine-like activity, but with approximately 1,000 times the activity of morphine. Usually, the compound was used in conjunction with a tranquilizer and scopolamine. The small dose required enabled M.99 to be administered by a projectile syringe of 2-ml. capacity. The effect of the immobilizing compound can be reversed with nalorphine or with compound M.285.