From: fzvfpu@gvnp.arg (Samson)
Subject: Re: tolerance reversal?
Date: 1997/05/30
Newsgroups: alt.drugs.hard

In article <338BD3CA.1E41@avana.net>, micro  wrote:

> on a dmx faq I read that dextromethorphan attenuates and reverses
> analgesic tolerance to morphine. has anyone heard of this?

Two views on the phenomenon are out there:

Title
       Dextromethorphan attenuates and reverses analgesic tolerance to
       morphine.
Author
       Elliott_K; Hynansky_A; Inturrisi_CE
Address
       Department of Pharmacology, Cornell University Medical
       College, New York, NY 10021.
Source
       Pain, 1994 Dec, 59:3, 361-8
Abstract
       Tolerance to the antinociceptive (analgesic) effect of morphine, a
       mu-opioid agonist, was developed in male CD-1 mice as
       assessed by a shift to the right of the analgesic (tail-flick)
       dose-response curves and an increase in the ED50 values.
       Administration of dextromethorphan at 30 mg/kg s.c., but not
       saline, 30 min prior to an escalating 3 times per day (t.i.d.)
       morphine dosing schedule prevented a 5-fold increase in the
       morphine ED50 value observed on treatment day 4. Concurrent
       administration of dextromethorphan at 12 mg/kg/24 h by s.c.
       infusion prevented the 6-fold increase in the morphine ED50
       value that was observed in control mice that received morphine at
       30 mg/kg/24 h by s.c. infusion. Implantation of two 25 mg
       morphine pellets resulted in a 10-fold increase in the morphine
       ED50 value on treatment day 4. Administration of
       dextromethorphan at 30 mg/kg s.c. t.i.d., but not saline, resulted
       in a reversal of morphine tolerance with the almost complete
       return of the morphine ED50 value to the control (opioid naive)
       value. These results demonstrate that dextromethorphan, an
       NMDA receptor antagonist can modulate morphine
       (mu-receptor)-mediated tolerance.

Title
       Dextromethorphan potentiates morphine antinociception, but does
       not reverse tolerance in rats.
Author
       Hoffmann_O; Wiesenfeld-Hallin_Z
Address
       Karolinska Institute, Department of Medical Laboratory Sciences
       and Technology, Huddinge University Hospital, Sweden.
Source
       Neuroreport, 1996 Feb 29, 7:3, 838-40
Abstract
       The N-methyl-D-aspartate (NMDA) and cholecystokinin
       (CCK)-B receptors may have a role in the development and
       reversal of tolerance to morphine. In morphine-tolerant rats,
       addition of the CCK-B receptors antagonist CI 988 or the NMDA
       receptor blocker dextromethorphan enhanced the antinociceptive
       effect of morphine on the hot plate test. However, combined
       administration of CI 988 and dextromethorphan did not further
       potentiate the antinociceptive effect of morphine in tolerant rats.
       Dextromethorphan by itself had no effect in tolerant rats. In
       drug-naive rats, dextromethorphan by itself had no
       antinociceptive effect, but when combined with morphine or
       morphine and CI 988, it significantly potentiated the magnitude
       and duration of the effect of morphine. Thus, unlike the reversal
       of tolerance with CI 988 at doses that did not potentiate the effect
       of morphine, the antinociception observed with the NMDA
       antagonist in the presence of morphine in tolerant rats may not
       represent the reversal of tolerance, but may instead reflect the
       potentiation of morphine's analgesic effect by dextromethorphan.

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