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New Benzopyrans: Anticonvulsant Activities

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The Therapeutic Potential Of Marihuana

Summary

Three new analogs of dimethylheptylpyran (DMHP) (SP-141, SP-143, and SP-175) were found to exhibit significant anticonvulsant activity against audiogenic, supramaximal electroshock, and maximal pentylentetrazol induced seizures in mice. In rats, all three compounds were found to be more active than diphenylhydantoin in the supramaximal electroshock test. In particular, a different profile of anticonvulsant activity was demonstrated for SP-175 compared to DMHP or delta-9-THC. It was discovered in 5-day studies that dilantin, phenobarbital, DMHP, and SP-175 do not exhibit tolerance development against audiogenic seizures in mice.

NOTE: We would like to express our appreciation to Dr. Harvey Kupferberg and the Anticonvulsant Advisory Committee of the National Institute of Neurological Diseases and Stroke for their encouragement of this study (supported in part by contract N01-NS-3-2314.)

The authors are indebted to Dr. R. K. Razdan, B. Zitko Terris, and H. G. Pars of the John C. Sheehan Institute for Research and Sharps Associates (SISA), Cambridge, Massachusetts, for the original chemical preparation of the three derivatives of DMHP.

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References

  • Boggan, W.O., Steele, R.A., & Freedman, D.X. Delta-9-tetrahydrocannabinol effect on audiogenic seizure susceptibility., Psychopharmacologia, 1973, 29, 101–106.

    Article  PubMed  CAS  Google Scholar 

  • Carlini, E.A., Leite, J.R., Tannhauser, M., & Berardi, A. C. Cannabidiol and Cannabis sativa extract protect mice and rats against convulsive agents. Psychopharmacologia, 1973, 25, 664–665.

    CAS  Google Scholar 

  • Chesher, G.B., & Jackson, D.M. Anticonvulsant effects of cannabinoids in mice: Drug interactions within cannabinoids and cannabinoid interactions with phenytoin. Psychopharmacologia, 1974, 37, 255–264.

    Article  PubMed  CAS  Google Scholar 

  • Consroe, P.F., & Man, D.P. Effects of delta-8-and delta-9-tetrahydrocannabinol on experimentally induced seizures. Life Sci., 1973, 13, 429-439.

    Google Scholar 

  • Corcoran, M.E., McCaughran, J.A., Jr., & Wada, J.A. Acute antiepileptic effects of delta-9-tetrahydrocannabinol in rats with kindled seizures. Exp. Neurol., 1973, 40, 471–483.

    Article  PubMed  CAS  Google Scholar 

  • Davis, J.P., & Ramsey, H. H. Antiepileptic action of marihuana-active substances. Fed. Proc., 1949, 8, 284–285.

    Google Scholar 

  • Domino, E.F., Hardman, H.F., & Seevers, M.H. Central nervous system actions of some synthetic tetrahydrocannabinol derivatives., Pharmacol. Rev., 1971, 23, 317–336.

    PubMed  CAS  Google Scholar 

  • Domino, E.F. Neuropsychopharmacologic studies of marijuana: Some synthetic and natural THC derivatives in animals and man. Ann. N.Y. Acad. Sci., 1971, 191, 166–192.

    Article  CAS  Google Scholar 

  • Frey, H.H., & Kretschmer, B.H. Anticonvulsant effect of trimethadione during continued treatment in mice. Arch. Int. Pharmacodyn., 1971, 193, 181–190.

    PubMed  CAS  Google Scholar 

  • Frey, H.H., & Kampmann, E. Tolerance to anticonvulsant drugs. Acta Pharmacol, and Toxicol., 1965, 22, 159–171.

    Article  CAS  Google Scholar 

  • Fried, P.A., & McIntyre, D.C. Electrical and behavioral attenuation of the anticonvulsant properties of delta-9-THC following chronic administrations. Psychopharmacologia, 1973, 31, 215–227.

    Article  PubMed  CAS  Google Scholar 

  • Garriott, J.D., Forney, R.B., Hughes, F.W., & Richards, A.B. Pharmacological properties of some cannabis related compounds. Arch. Int. Pharmacodyn., 1968, 171, 425–434.

    PubMed  CAS  Google Scholar 

  • Hardman, H.F., Domino, E.F., & Seevers, M.H. General pharmacological actions of some synthetic tetrahydrocannabinol derivatives. Pharmacol. Rev., 1971, 23, 295–315.

    PubMed  CAS  Google Scholar 

  • Karler, R. Anticonvulsant activity of delta-9-tetrahydrocannabinol. Fed. Proc., 1973, 32, 756.

    Google Scholar 

  • Karler, R., Cely, W., & Turkanis, S.A. The anticonvulsant activity of cannabidiol and cannabinol. Life Sci., 1973, 13, 1527–1531.

    Article  PubMed  CAS  Google Scholar 

  • Karler, R., Cely, W., & Turkanis, S.A. A study of the relative anticonvulsant and toxic activities of delta-9-tetrahydrocannabinol and its congeners. Res. Commun, Chem. Pathol. Pharmac., 1974, 7, 353–358(a).

    CAS  Google Scholar 

  • Karler, R., Cely, W., & Turkanis, S.A. Anticonvulsant properties of delta-9-tetrahydrocannabinol and other cannabinoids. Life Sci., 1974, 15, 931–947(b).

    Article  PubMed  CAS  Google Scholar 

  • Karler, R., Cely, W., & Turkanis, S.A. A study of the development of tolerance to an anticonvulsant effect of delta-9-tetrahydrocannabinol and cannabidiol. Res. Commun. Chem. Path. Pharmac., 1974, 9, 23–39(c).

    CAS  Google Scholar 

  • Killam, K.F., & Killam, E.K. The action of tetrahydrocannabinol on EEG and photomyoclonic seizures in the baboon. Fifth Into Cong. Pharm., Basel, Switz., 1972, 124.

    Google Scholar 

  • Kinnard, W.J., & Carr, C.J. A preliminary procedure for the evaluation of central nervous system depressants. J. Pharmacol. Exp. Therap., 1957, 121, 354–361.

    CAS  Google Scholar 

  • Loewe, S., & Goodman, L.S. Anticonvulsant action of marijuana-active substances. Fed. Proc., 1947, 6, 352.

    Google Scholar 

  • Man, D.P., & Consroe, P.F. Effects of delta-9-tetrahydrocannabinol on experimentally induced seizures. J. Int. Res. Commun., 1973, 1, 12.

    Google Scholar 

  • O’shaughnessy, W.B. On the preparation of the Indian hemp or gunjah (Cannabis indica): The effect on the animal system in health, and their utility in the treatment of tetanus and other convulsive diseases. Trans, Med. Phys. Soc., Bombay, 1842, 8, 421–461.

    Google Scholar 

  • Plotnikoff, N.P., & Green, D.M. Bioassay of potential ataraxic agents against audiogenic seizures in mice. J. Pharmacol. Exp. Therapy, 1957, 119, 294–298.

    CAS  Google Scholar 

  • Plotnikoff, N.P., Zaugg, H., Petersen, A.C., Anderson, R., & Arendsen, D. Anticonvulsant activity of new benzopyrans0 Abstracts of 168th ACS National Meeting, Atlantic City, N.J., September 9–12, 1974.

    Google Scholar 

  • Plotnikoff, N.P., Zaugg, H.E., Petersen, A.C., Arendsen, D.L., & Anderson, R.F. New benzopyrans: Anticonvulsant activities. The Pharmacologist, Fall, 1975, 17, 2, 177(a).

    Google Scholar 

  • Plotnikoff, N.P., Zaugg, H.E., Petersen, A.C., Arendsen, D.L., & Anderson, R.F. New benzopyrans: Anticonvulsant activities. Life Sci., 1975, 17, 97–104(b).

    Article  PubMed  CAS  Google Scholar 

  • Razdan, R.K., Terris, B.Z., & Pars, H.G. Manuscript in preparation (Compounds SP-175, SP-141, SP-143), 1975.

    Google Scholar 

  • Sofia, R.D., Solomon, T.A., & Barry, H., III. The anticonvulsant activity of delta-9-tetrahydrocannabinol in mice. Pharmacologist, 1971, 13, 246.

    Google Scholar 

  • Swinyard, E.A., Brown, W.C., & Goodman, L.S. Comparative assays of antiepileptic drugs in mice and rats, J. Pharmacol. Exp. Therapy, 1952, 106, 3l9–330.

    Google Scholar 

  • Toman, E.P., & Everett, G.M. Anticonvulsants in evaluation of drug activities (Ch. 13), Pharmacometrics, vol. 1. New York: Academic Press, 1964.

    Google Scholar 

  • Wada, J.A., Sato, M. & Corcoran, M.E. Antiepileptic properties of delta-9-tetrahydrocannabinol. Exp. Neurol., 1973, 39, 157–165.

    Article  PubMed  CAS  Google Scholar 

  • Woodbury, D.M., Penry, J.K., & Schmidt, R.P. Antiepileptic drugs. New York: Raven Press, 1972.

    Google Scholar 

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© 1976 Plenum Publishing Corporation

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Plotnikoff, N.P. (1976). New Benzopyrans: Anticonvulsant Activities. In: Cohen, S., Stillman, R.C. (eds) The Therapeutic Potential Of Marihuana. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-4286-1_34

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  • DOI: https://doi.org/10.1007/978-1-4613-4286-1_34

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-4288-5

  • Online ISBN: 978-1-4613-4286-1

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