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Oral administration of dextromethorphan prevents the development of morphine tolerance and dependence in rats
Mao, Jianren*,a; Price, Donald D.a; Caruso, Frank S.b; Mayer, David J.a
aDepartment of Anesthesiology, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA 23298 USA
bAlgos Pharmaceutical Corporation, Collingwood Plaza, 4900 Route 33, Neptune, NJ 07753 USA
*Corresponding author: Dr. Jianren Mao, Department of Anesthesiology, Medical College of Virginia, Box 980516, Richmond, VA 23298, USA. Tel.: (804) 8285336; Fax: (804) 8284023.
(Received 10 May 1995; revised version received 6 February 1996; accepted 21 February 1996.)
Abstract
Combined oral administration of morphine sulfate (MS) and the over-the-counter antitussive drug and N-methyl-D-aspartate receptor antagonist dextromethorphan (DM) prevented the development of tolerance to the antinociceptive effects of MS (15, 24, or 32 mg/kg) in rats. This combined oral treatment regimen also attenuated signs of naloxone-precipitated physical dependence on morphine in the same rats. A wide range of ratios of MS to DM (2:1, 1:1, and 1:2) were effective for preventing the development of morphine tolerance and dependence. In addition, we provide evidence that under certain circumstances DM increases the acute antinociceptive effects of MS. All of these results indicate that oral treatment that combines DM with opiate analgesics may be a powerful approach for simultaneously preventing opiate tolerance and dependence and enhancing analgesia in humans.