Protective effects of calcium-magnesium soft gels in morphine tolerant and dependent mice.
The present study was aimed at evaluating the acute effects of Calcium-Magnesium soft gels (CalMag) in morphine tolerant and dependent mice. Mice were rendered tolerant and dependent on morphine by subcutaneous injection of morphine over a fixed time period. Withdrawal signs were precipitated by injecting naloxone 2 h after the final injection of morphine. The tail-pinch assay was used to investigate the effects of various compounds on the development and reversal of morphine tolerance. Acute injection of CalMag (containing 50 mg/kg calcium and 25 mg/kg magnesium) significantly reduced the number of jumps, stands and fast breathing in morphine dependent mice. Co-administration of calcium (50 mg/kg) and magnesium (25 mg/kg) was also effective in preventing the development of morphine tolerance and dependence. Administration of calcium (up to 50 mg/kg) alone did not significantly block the development of tolerance and dependence. The mean latency to pain was significantly increased in animals pretreated with CalMag (containing 50 mg/kg calcium and 25 mg/kg magnesium). The mixture of calcium and magnesium at specific concentrations seem to be critical for preventing the development of morphine tolerance and dependence.
Rabbani
M
M
Department of Pharmacology, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran. rabbani@pharm.mui.ac.ir
Sadeghi
H M
HM
Gudarzi
S
S
D000818:Animals; D002118:Calcium / Q000008:administration & dosage / Q000378:metabolism*; D004361:Drug Tolerance; D005782:Gels; D008274:Magnesium / Q000008:administration & dosage / Q000378:metabolism*; D008297:Male; D051379:Mice; D009020:Morphine / Q000008:administration & dosage; D009021:Morphine Dependence / Q000517:prevention & control*; D009270:Naloxone / Q000008:administration & dosage / Q000378:metabolism; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000378:metabolism; D010147:Pain Measurement; D020011:Protective Agents / Q000008:administration & dosage / Q000378:metabolism; D013375:Substance Withdrawal Syndrome / Q000517:prevention & control*
D005782:Gels; D009292:Narcotic Antagonists; D020011:Protective Agents; D009270:Naloxone; D009020:Morphine; D008274:Magnesium; D002118:Calcium