We investigated the ability of dextromethorphan, a clinically available NMDA receptor antagonist, to attenuate the behaviors and the expression of c-fos mRNA associated with acute morphine withdrawal in the 7-day-old rat. The intensity of the acute morphine withdrawal behaviors and the elevation in c-fos mRNA expression in the brain induced by acute morphine withdrawal were reduced by dextromet...

Dextromethorphan is a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist known to inhibit wind-up and central hyperexcitability of dorsal horn neurones. We studied 24 healthy, unmedicated male volunteers, aged 21-28 yr, in a randomized, double-blind, placebo-controlled, crossover study. Burn injuries were produced on the medial surface of the dominant calf with a 25 x 50 mm rectang...

The main aim of this study was to evaluate the effects of dextromethorphan and midazolam and their combination on morphine tolerance and dependence in mice. In the present study, different groups of mice were rendered randomly and received morphine (50 mg kg(-1), s.c.), morphine (50 mg kg(-1), s.c.) + Dextromethorphan (25, 50 and 75 mg kg(-1), i.p.), morphine (50 mg kg(-1), s.c.) + midazolam (0...

OBJECTIVES To analyze the trend of dextromethorphan abuse in California and to compare these findings with national trends. DESIGN A 6-year retrospective review. SETTING California Poison Control System (CPCS), American Association of Poison Control Centers (AAPCC), and Drug Abuse Warning Network (DAWN) databases from January 1, 1999, to December 31, 2004. PARTICIPANTS All dextromethorpha...

Experimental ischemia models have shown the antitussive dextromethorphan to be an N-methyl-D-aspartate antagonist with neuroprotective properties. We treated 10 patients with a history of recent stroke or transient ischemic attack with oral dextromethorphan (60 mg q.i.d.) for 3 weeks in a placebo-controlled, double-blind, crossover tolerance study. We documented no clinical evidence of toxicity...

Although the residues that determine the preference of CYP2D6 (cytochrome P450 2D6) for compounds containing a basic nitrogen are well characterized, the contribution of other active site residues to substrate binding and orientation is less well understood. Our structural model of CYP2D6 identifies the aromatic residue Phe120 as a likely major feature of the active site. To examine the role of...

Predicting the magnitude of potential drug-drug interactions is important for underwriting patient safety in the clinical setting. Substrate-dependent inhibition of cytochrome P450 enzymes may confound extrapolation of in vitro results to the in vivo situation. However, the potential for substrate-dependent inhibition with CYP2D6 has not been well characterized. The inhibition profiles of 20 kn...

Background. Dextromethorphan is a noncompetitive N-methyl D-aspartate receptor antagonist that is clinically feasible for relieving the opioid withdrawal symptoms. This study compares the efficacy of a combination therapy with dextromethorphan and clonidine to treatment with clonidine alone. Methods and Materials. In this double-blind randomized clinical trial, patients were selected from inpat...