Pharmacology of methadone and its isomers
by
Inturrisi CE.
Department of Pharmacology,
Weill Medical College of Cornell University,
New York, NY, USA.
Minerva Anestesiol. 2005 Jul-Aug;71(7-8):435-7.

ABSTRACT

Methadone is a synthetic opioid analgesic that is used as an alternate to morphine and hydromorphone for patients with severe pain. It is increasingly being used in opioid rotation schedules. Methadone has an asymmetric carbon atom resulting in 2 enantiomeric forms, the d and l isomers. The racemic mixture (dl-methadone) is the form commonly used clinically. Recent studies have revealed the pharmacological activity of the d-methadone isomer. We found that the d isomer of methadone has N-methyl-D-aspartate (NMDA) receptor antagonist activity both in vitro and in vivo. Studies were designed to examine the ability of d-methadone to attenuate the development of morphine tolerance and to modify NMDA-induced hyperalgesia in rats. Repeated dosing with intrathecal morphine produced a 38-fold increase in the morphine ED50 value. This decrease in the potency of morphine was completely prevented by the coadministration of intrathecal d-methadone at 160 mug/rat. In addition, the decrease in thermal paw withdrawal latency induced by the intrathecal administration of 1.64 mug/rat NMDA was completely blocked by pretreatment with 160 mug/rat d-methadone. Thus, the same dose of intrathecal d-methadone that attenuates the development of spinal morphine tolerance blocks NMDA-induced hyperalgesia in rats. These results support the CONCLUSIONS: that d-metha-done affects the development of morphine tolerance and NMDA-induced hyperalgesia by virtue of its NMDA receptor antagonist activity.

Methadone
Methadone maintenance
Methadone and cancer pain
Methadone: "killer drug" etc
Buprenorphine v methadone
Methadone, LAAM and the rush
Methadone for tramadol addicts?
Methadone/morphine as antidepressants

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