nalorphine and methylnaltrexone

A sensitive taste conditioning test was used to measure the aversive effect of a single intraventricular (i.c.v.) or subcutaneous (s.c) injection of an opioid antagonist that readily crosses the blood brain barrier (naltrexone), and one of two that do not (methylnaltrexone and diallylnormorphinium). This was done in drug-naive rats and in rats implanted 5 days earlier with a pellet containing 75 mg morphine. It was found that the morphine exposure had no significant effect on the dose-response curve of the taste aversion produced by s.c. methylnaltrexone and s.c. diallynormorphinium but reduced the lowest effective dose for the other antagonist treatments from three to more than 100 times. Consideration of the data, together with the pharmacokinetic properties of the drugs and the routes of administration used, supported a conclusion that only those aversions involving central antagonist activity show the potentiation effect of chronic morphine treatment. The findings were also discussed with regard to the location of receptors important for aversions produced by opioid antagonists in naive rats.

Topics: Animals; Blood-Brain Barrier; Dose-Response Relationship, Drug; Drug Synergism; Infusions, Parenteral; Injections, Subcutaneous; Male; Morphine Dependence; Nalorphine; Naltrexone; Narcotic Antagonists; Quaternary Ammonium Compounds; Rats; Rats, Inbred Strains; Taste

Naloxone was found to provoke a hypotensive effect related to the dose on high blood pressure (BP) induced by short-term isolation in young rats. Another opiate antagonist, nalorphine, also reduced the arterial pressure of socially deprived rats. In contrast, naltrexone methylbromide that selectively blocked peripheral opiate receptors did not alter the elevated BP. To investigate whether adrenomedullary opioids were somehow implicated in the development of isolation-induced hypertension, bilaterally adrenalectomized rats were kept under social deprivation for 7 consecutive days. The data obtained indicated that high systolic BP developed in the same manner as in intact rats run in parallel. In conclusion, central opioids appear to be involved in BP elevation due to the stress generated by brief social deprivation in young rats.

Topics: Adrenalectomy; Animals; Blood Pressure; Corticosterone; Endorphins; Gastrointestinal Motility; Male; Morphine; Nalorphine; Naloxone; Naltrexone; Quaternary Ammonium Compounds; Rats; Rats, Inbred Strains; Social Isolation; Stress, Physiological