Reduction of morphine dependence and potentiation of analgesia by chronic co-administration of nifedipine.
Nifedipine, 5 mg/kg IP, potentiated the morphine-induced analgesia measured in the hot-plate, but not in the tail-flick test. Further experiments were carried out using the hot-plate test only. Pretreatment with nifedipine partially restores the analgesic action of morphine in morphine-tolerant rats. Co-administration of nifedipine with morphine in a chronic experiment did not prevent the loss of morphine efficiency (an increase in latency of 44% was not significant) and did not prevent the debilitating effect of chronic morphine administration reflected by an inhibition of the body weight gain, but prevented naloxone-induced withdrawal syndrome (quantified by counting head shakes) in the test carried out 24 h after the injection of nifedipine, when the drug did not affect morphine analgesia. Chronic treatment with either morphine or nifedipine did not produce a significant increase in the density of [3H] naloxone or [3H]prazosin binding sites in the cortex and in the rest of the brain (measured 24 h after the last dose), but the combined treatment resulted in a significant increase in the cortical [3H]prazosin binding site density. The present results suggest that opiate tolerance and physical dependence may be separated by co-administration of nifedipine and suggest that the combined chronic treatment with morphine and nifedipine may increase the efficacy of morphine during chronic treatment and prevent development of abstinence.
Antkiewicz-Michaluk
L
L
Institute of Pharmacology, Polish Academy of Sciences, Kraków.
Michaluk
J
J
Romańska
I
I
Vetulani
J
J
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D004347:Drug Interactions; D004361:Drug Tolerance; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009021:Morphine Dependence / Q000523:psychology*; D009543:Nifedipine / Q000494:pharmacology*; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects; D011957:Receptors, Opioid / Q000187:drug effects; D017450:Receptors, Opioid, mu / Q000187:drug effects; D013375:Substance Withdrawal Syndrome / Q000523:psychology; D015430:Weight Gain / Q000187:drug effects
D000700:Analgesics; D018340:Receptors, Adrenergic, alpha-1; D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; D009020:Morphine; D009543:Nifedipine