Dextrorphan

Abstract: The characteristics of the interaction between dihydromorphine (DHM) and a synaptic plasma membrane (SPM) fraction from rat brain cerebral cortex have been studied. DHM at 10+9 M concentration is bound in a reversible process which is partly specific. The specific binding is inhibited by the sulphydryl reagents, N-ethylmaleimide and p-chloromercuribenzoic acid. The binding is strongly inhibited by 10−8 M levorphanol but significantly less inhibited by its optical antipode, dextrorphan, which is much less analgetic. At 10−8 M concentration, nalorphine and naloxone were strongly inhibitory while heroin at 10−8 M and codeine at 10−7 M were nearly inactive. A mixture of 10−5 M acetylcholine and 2.5 × 10−5 M eserine caused a moderate inhibition while dopamine, noradrenaline, serotonin, histamine and propranolol were classified as inactive (i. e. caused less than 25 % inhibition at 10−5 M). The observed binding characteristics of the SPM fraction are compatible with those which might be expected for the actual narcotic receptor. Analogous SPM preparations from subcortical parts of the cerebrum and from the brain stem also showed stereospecific binding of narcotics.

Abstract: Neuropathic pain remains a significant clinical problem. Current understanding implicates the spinal cord dorsal horn N-methyl-d-aspartate (NMDA) receptor apparatus in its pathogenesis. Previous reports have described NMDA antagonist reduction of nerve injury-induced thermal hyperalgesia and formalin injection-related electrical activity. We examined a panel of spinally administered NMDA antagonists in two models: allodynia evoked by tight ligation of the fifth and sixth lumbar spinal nerves (a model of chronic nerve injury pain), and the formalin paw test (a model wherein pretreatment with drug may preempt the development of a pain state). A wide range of efficacies was observed. In the nerve injury model, order of efficacy (expressed as percent of maximum possible effect +/- S.E.), at the maximum dose not yielding motor impairment, was memantine (96 +/- 5%) = AP5 (91 +/- 7%) > dextrorphan (64 +/- 11%) = dextromethorphan (65 +/- 22%) > MK801 (34 +/- 8%) > ketamine (18 +/- 6%). For the formalin test, the order of efficacy was AP5 (86 +/- 9%) > memantine (74 +/- 5%) > or = MK801 (67 +/- 16%) > dextrorphan (47 +/- 16%) > dextromethorphan (31 +/- 12%) > ketamine (17 +/- 15%). In the nerve injury model, no supraspinal action was seen after intracerebroventricular injections of dextromethorphan and ketamine. NMDA antagonists by the spinal route appear to be useful therapeutic agents for chemically induced facilitated pain as well as nerve injury induced tactile allodynia. It is not known what accounts for the wide range of efficacies.

Abstract: In homogenate of rat brain, morphine, at concentrations obtainable in vivo, inhibited the stimulation by prostaglandin E1 or E2 of cyclic AMP formation, without inhibiting the basal production of cyclic AMP. Heroin was more atnd methadone less active than morphine, whereas dextrorphan was inactive and naloxone antagonised the effect of morphine. This inhibition may represent a mechanism whereby morphine-like drugs exert their analgesic or other effects.