Reduction of morphine dependence and potentiation of analgesia by chronic co-administration of nifedipine

Abstract

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.

The Ca2+ Channel Blockade Changes the Behavioral and Biochemical Effects of Immobilization Stress

“…Because the latter is regarded as at least a partial model for drug addiction (Roberts et al 1995), the present data suggest that L-type Ca 2ϩ channel blocking agents may be useful in the treatment of drug dependence. This, in fact, corroborates our previous studies demonstrating that morphine administration in the presence of nifedipine and other L-type Ca 2ϩ blockers prevents the ability of naloxone to induce withdrawal syndrome in rats chronically injected with morphine (Antkiewicz- Michaluk et al 1990Michaluk et al , 1993Michaluk et al 1998).…”

“…Previous studies have demonstrated that the increase in L-type Ca 2ϩ channel density is observed in a variety of conditions that produce an increase in responsiveness of rats to dopaminergic stimuli, such as repeated electroconvulsive shock (Antkiewicz- Michaluk et al 1990Michaluk et al , 1994b, morphine abstinence (Antkiewicz- Michaluk et al, 1993Michaluk et al, , 1994a or neuroleptic withdrawal (Mamczarz et al 1994, Antkiewicz-Michaluk et al 1995. Co-administration of nifedipine with those treatments inhibits their propensity to produce of various changes, believed to be of adaptive character.…”

Changes In Liver and Brain Cytochrome P450 after Multiple Cocaine Administration, Alone and in Combination with Nifedipine

“…Both compounds, applied alone or in combination, did not significantly change the quantity of brain cytochrome P450. DISCUSSION L-type calcium channel blockers of the dihydropyridine class, such as nifedipine, nimodipine, amlodipine, have been reported to affect different types of drug dependence and withdrawal, including those to opioides (15), alcohol (16), psychostimulants (10). At the same time they are known to be the substrates of one of the most abundant cytochrome P450 isoenzyme CYP3A that interacts with other substrates of this isoform, including cocaine.…”

Inhibition of Evoked Glutamate Release by Neurosteroid Allopregnanolone Via Inhibition of L-Type Calcium Channels in Rat Medial Prefrontal Cortex

“…L-type calcium channels have been found to regulate a multitude of neuronal processes including neurotransmitter release, gene expression, mRNA stability, neuronal survival, ischemic-induced axonal injury, synaptic efficacy, and the activity of other ion channels (Lipscombe et al, 2004), but it appears that there may be a different role of L-type calcium channels in different brain regions, especially for the effect on neurotransmitter release (Lipscombe et al, 2004;Li and Bennett, 2003;Wiser et al, 1999;Sabria et al, 1995;Reuter, 1996;Lopez et al, 2001;Bargas et al, 1998). In addition, it was reported that some pathophysiologic stimulus such as stress and psychostimulants could significantly elevate the expression of L-type calcium channels in the cerebral cortex (ntkiewicz-Michaluk et al, 1990(ntkiewicz-Michaluk et al, , 1993(ntkiewicz-Michaluk et al, , 1994a(ntkiewicz-Michaluk et al, , b, 1995Mamczarz et al, 1994Mamczarz et al, , 1999 and this elevation had been proposed to be involved in etiology of a variety of psychiatric disorders such as schizophrenia, morphine abstinence, and neuroleptic withdrawal (ntkiewicz-Michaluk et al, 1994a(ntkiewicz-Michaluk et al, , b, 1997(ntkiewicz-Michaluk et al, , 1995(ntkiewicz-Michaluk et al, , 1993Mamczarz et al, 1994Mamczarz et al, , 1999. Moreover, the glutamate release in the medial prefrontal cortex is also important in etiology of a variety of psychiatric disorders Moghaddam et al, 1997;Moghaddam and Adams, 1998).…”