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Cellular and Molecular Neurobiology

, Volume 8, Issue 2, pp 149–156 | Cite as

Dextromethorphan binding sites in the guinea pig brain

  • José M. Musacchio
  • Martine Klein
Review

Summary

  1. 1.

    Dextromethorphan (DM), a dextrorotatory nonopioid antitussive, binds to specific high-affinity sites in the central nervous system. These sites are distinct from the opioid and other known neurotransmitter receptor sites. Antitussives such as carbetapentane and caramiphen also bind to DM sites with a nanomolar affinity.

     
  2. 2.

    The anticonvulsant drugs phenytoin and ropizine produce an allosteric enhancement of the binding of [3H]DM to guinea pig brain. DM, carbetapentane, and caramiphen also are efficacious anticonvulsant agents in the rat maximal electroshock seizures test, and DM enhances the anticonvulsant effects of phenytoin (PHT).

     
  3. 3.

    These results suggest that drugs that bind to the DM sites could be used alone as anticonvulsants or in combination with PHT to lower its effective dose and reduce its side effects.

     
  4. 4.

    The investigation of the DM binding sites may help to open new approaches for the treatment of convulsive disorders and to explain further some of the molecular mechanisms of neutronal excitability.

     

Key words

anticonvulsant activity dextromethorphan dextromethorphan binding sites ion channels phenytoin 

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References

  1. Craviso, G. L., and Musacchio, J. M. (1983a). High affinity dextromethorphan binding sites in guinea-pig brain. I. Initial characterization.Mol. Pharmacol. 23619–628.Google Scholar
  2. Craviso, G. L., and Musacchio, J. M. (1983b). High affinity dextromethorphan binding sites in guinea-pig brain. II. Competition experiments.Mol. Pharmacol. 23629–640.Google Scholar
  3. Desmedt, L. K. C., Niemegeers, C. J. E., and Janssen, P. A. J. (1975). Anticonvulsive properties of cinnarizine and flunarizine in rats and mice.Arzneimittel-Forsch. 251408–1413.Google Scholar
  4. Klein, M., Santiago, L. J., and Musacchio, J. M. (1987). Effect of calcium and other ion channel blocking agents on the high affinity binding of dextromethorphan to guinea pig brain.Soc. Neurosci. Abstr. 131157.Google Scholar
  5. Reynolds, I. J., Snowman, A. M., and Snyder, S. H. (1986). (−)[3H]Desmethoxyverapamil labels multiple calcium channel modulator receptors in brain and skeletal muscle membranes: Differentiation by temperature and dihydropyridine.J. Pharmacol. Exp. Ther. 237731–738.Google Scholar
  6. Santiago, L. J., Klein, M., and Musacchio, J. M. (1987). Effect of anticonvulsant drugs and other agents on the high affinity binding of dextromethorphan to guinea pig brain.Soc. Neurosci. Abstr. 131157.Google Scholar
  7. Tortella, F. C., and Musacchio, J. M. (1986a). Non-opioid antitussives: Anticonvulsant profile against maximal electroshock (MES) seizures.Fed. Proc: 45677.Google Scholar
  8. Tortella, F. C., and Musacchio, J. M. (1986b). Dextromethorphan and carbetapentane: Centrally acting non-opioid antitussive agents with novel anticonvulsant properties.Brain Res. 383314–318.Google Scholar
  9. Tortella, F. C., and Musacchio, J. M. (1987). Caramiphen edisylate: A non-opioid antitussive with potent anticonvulsant activity.Fed. Proc. 46708.Google Scholar
  10. Treiman, D. M., Wilensky, A. J., Ben-Menachen, E., Ojemann, L., Yerby, M., O'Leary Barber, K., McCormick, K. B., Cereghino, J. J., White, B. G., and Swisher, K. (1985). Efficacy of nafimidone in the treatment of intractable partial seizures: Report of a two-center pilot study.Epilepsia 26607–611.Google Scholar
  11. Walker, K. A. M., Wallach, M. B., and Hirschfeld, D. R. (1981). 1-(Naphthylalkyl)-1 H-imidazole derivatives, a new class of anticonvulsant agents.J. Med. Chem 2467–74.Google Scholar

Copyright information

© Plenum Publishing Corporation 1988

Authors and Affiliations

  • José M. Musacchio
    • 1
  • Martine Klein
    • 1
  1. 1.Department of PharmacologyNew York University Medical CenterNew YorkUSA

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