Skip to main content

Psychopharmacological studies on (-)-nuciferine and its Hofmann degradation product atherosperminine

Abstract

(-)-Nuciferine and its Hofmann degradation product atherosperminine showed divergent psychopharmacological effects. Because nuciferine has been reported to be a neuroleptic and atherosperminine has some chemical resemblance to dopamine, they were investigated for their dopamine-receptor activities. Nuciferine had a pharmacologic profile of action associated with dopamine-receptor blockade; i.e., it induced catalepsy, inhibited spontaneous motor activity, conditioned avoidance response, amphetamine toxicity and stereotypy. On the other hand, atherosperminine produced effects associated with dopamine receptor stimulation, i.e., stereotypy, increase in spontaneous motor activity and amphetamine toxicity, reversal of haloperidol-induced catalepsy and inhibition of conditioned avoidance response, inhibition of morphine analgesia, and potentiation of the anticonvulsant action of diphenylhydantoin. The results are discussed on the basis of the chemical configuration of the two compounds.

This is a preview of subscription content, access via your institution.

References

  • Bick, I. R. C., Douglas, G. K.: The alkaloids of Atherospermum moschatum Labill. II. Non-phenolic alkaloid. Aust. J. Chem. 18, 1997–2004 (1965)

    Google Scholar 

  • Bhattacharya, S. K., Bose, R.: Role of brain monoamines and acetylcholine in morphine induced catalepsy in rats. In: Proceedings of the symposium on Drugs and biogenic amines, p. 30. Jaipur: Department of Pharmacology S.M.S. Medical College 1976

    Google Scholar 

  • Bhattacharya, S. K., Jaiswal, B. K., Reddy, P. K. S. P., Das, P. K.: Studies on the role of brain monoamines in the antinociceptive action of morphine in albino rats. Indian J. Pharmacol. 7, 58–68 (1975)

    Google Scholar 

  • Bhattacharya, S. K., Sanyal, A. K., Ghosal, S.: Studies on the role of brain monoamines in the potentiation of morphine analgesia by monoamine oxidase inhibitors nialamide and mangiferin in albino rats. In: Drugs and central synaptic transmission, P. B. Bradley and B. N. Dhawan, eds., p. 333. London: Macmillan 1976a

    Google Scholar 

  • Bhattacharya, S. K., Reddy, P. K. S. P., Das, P. K.: Studies on the role of brain monoamines in the anticonvulsant action of diphenylhydantoin and nialamide potentiation of diphenylhydantoin in albino rats. In: Drugs and central synaptic transmission, P. B. Bradley and B. N. Dhawan, eds., p. 155. London: Macmillan 1976b

    Google Scholar 

  • Bhattacharya, S. K., Pandey, V. B., Ray, A. B., Dasgupta, B.: Neuropsychopharmacological studies with (-)-tetrahydrocoptisine. Arzneim. Forsch. 26, 2187–2190 (1976c)

    Google Scholar 

  • Brucke, F. Th. V., Hornykiewicz, O., Sigg, E. B.: The pharmacology of psychotherapeutic drugs, p. 3. New York: Springer 1966

    Google Scholar 

  • Cannon, J. G., Khonje, P. R., Long, J. P.: Centrally acting emetics 9. Hofmann and Emde degradation products of nuciferine. J. Med. Chem. 18, 110–112 (1975)

    Google Scholar 

  • Chopra, R. N., Chopra, I. C., Handa, K. L., Kapur, L. D.: Indigenous drugs of India, p. 606. Calcutta: Dhur 1958

    Google Scholar 

  • Chopa, R. N., Nayar, S. L., Chopra, I. C.: Glossary of Indian medicinal plants, p. 174. New Delhi: CSIR 1956

    Google Scholar 

  • Cook, L., Weidley, E.: Behavioural effects of some psychopharmacological agents. Ann. N. Y. Acad. Sci. 66, 740–752 (1957)

    Google Scholar 

  • Courvoisier, S., Fournel, R., Ducrot, M., Kolsky, M., Koetschet, P.: Proprietes pharmacodynamiques du chlorhydrate de chloro-3-(dimethylamino-3-propyl)-10 phenothiazine (4560 R. P.). Arch. Int. Pharmacodyn. Ther. 92, 305–361 (1953)

    Google Scholar 

  • Davies, J. A., Jackson, B., Redfern, P. H.: The effect of antiparkinsonism drugs on haloperidol induced inhibition of the conditioned avoidance response in rats. Neuropharmacology 12, 735–740 (1973)

    Google Scholar 

  • Davies, O. L., Raventos, J., Walpole, A. L. A method for evaluation of analgesic activity using rats. Br. J. Pharmacol. Chemother. 1, 255–264 (1946)

    Google Scholar 

  • Dews, P. B.: The measurement of the influence of drugs on voluntary activity in mice. Br. J. Pharmacol. Chemother. 8, 46–48 (1953)

    Google Scholar 

  • Ernst, A. M.: Mode of action of apomorphine and dexamphetamine in gnawing compulsion in rats: Psychopharmacologia (Berl.) 10, 316–323 (1967)

    Google Scholar 

  • Ernst, A. M., Smelik, P. G.: Site of action of dopamine and apomorphine in gnawing compulsion behaviour in rats. Experientia 22, 837–838 (1968)

    Google Scholar 

  • Fog, R.: On stereotypy and catalepsy: studies on the effects of amphetamine and neuroleptics in rats. Acta Neurol. Scand. [Suppl. 50] 48, 1–66 (1972)

    Google Scholar 

  • Fog, R., Randrup, A., Pakkenberg, H.: Neuroleptic action of quaternary chlorpromazine and related drugs injected into various brain areas in rats. Psychopharmacologia (Berl.) 12, 428–432 (1968)

    Google Scholar 

  • Fog, R., Randrup, A., Pakkenberg, H.: Intrastriatal injection of quaternary butyrophenones and oxypertine. Neuroleptic effects in rats. Psychopharmacologia (Berl.) 19, 224–230 (1971)

    Google Scholar 

  • Genovese, E., Zonta, N., Mantegazza, P.: Decreased antinociceptive activity of morphine in rats pretreated intraventricularly with 5,6-dihydroxytryptamine, a long lasting selective depletor of brain serotonin. Psychopharmacologia (Berl.) 32, 359–364 (1973)

    Google Scholar 

  • Glowinski, J.: Effects of amphetamines on various aspects of catecholamine metabolism in the central nervous system of the rat. In: Amphetamines and related compounds, E. Costa and S. Garattini, eds., p. 301. New York: Raven 1970

    Google Scholar 

  • Horn, A. S., Cuello, A. C., Miller, R. J.: Dopamine in the mesolimbic system of the rat brain. Endogenous levels and effects of drugs on the uptake mechanism and stimulation of adenylate cyclase activity. J. Neurochem. 22, 265–270 (1974)

    Google Scholar 

  • Janssen, P. A. J.: Is it possible to predict the clinical effects of neuroleptic drugs (major tranquilizers) from animal data; Arzneim. Forsch. 15, 104–117 (1965)

    Google Scholar 

  • Kirtikar, K. R., Basu, B. D.: Indian Medicinal Plants, Vol. 1, p. 116. New Delhi: Periodical Experts 1935

    Google Scholar 

  • Macko, E., Douglas, B., Weisbach, J. A.: Studies on the pharmacology of nuciferine and related aporphines. Arch. Int. Pharmacodyn. Ther. 197, 261–273 (1972)

    Google Scholar 

  • Major, C. T., Pleuvry, B. J.: Effect of α-methyl-p-tyrosine, p-chlorophenylalanine, 1-β-(3,4-dihydroxy)phenylalanine, 5-hydroxytryptophan and diethyldithiocarbamate on the analgesic action of morphine and methylamphetamine in the mouse. Br. J. Pharmacol. 42, 512–521 (1971)

    Google Scholar 

  • Miller, L. C., Tainter, M. L.: Estimation of ED50 and its error by means of logarithmic probit graph paper. Proc. Soc. Exp. Biol. Med. 57, 261–264 (1944)

    Google Scholar 

  • Nadkarni, A. K.: Indian Materia Medica, Vol. 1, p. 844. Bombay: Popular Prakashan 1954

    Google Scholar 

  • Pertwee, R. G.: The ring test — a quantitative method for assaying the cataleptic effect of cannabis in mice. Br. J. Pharmacol. 46, 753–763 (1972)

    Google Scholar 

  • Pinder, R. M., Buxton, D. A., Green, D. M.: On the dopamine-like action of apomorphine. J. Pharm. Pharmacol. 23, 995–996 (1971)

    Google Scholar 

  • Randrup, A., Munkvad, I.: Pharmacology and physiology of stereotyped behaviour. In: Catecholamines and their enzymes in the neuropathology of schizophrenia, S. Kety and S. Matthysse, eds., J. Psychiatr. Res. 11, 1 (1974)

  • Randrup, A., Munkvad, I., Fog, R., Ayhan, I. H.: Catecholamines in activation, stereotypy and level of mood. In: Catecholamines and behaviour, vol. 1, A. J. Friedhoff, ed., p. 89. New York: Plenum 1975

    Google Scholar 

  • Randrup, A., Munkvad, I., Scheel-Krüger, J.: Mechanisms by which amphetamines produce stereotypy, aggression and other behavioural effects In: Psychopharmacology of sexual disorders and drug abuse, T. Ban, ed. Prague: Avicenum 1973

    Google Scholar 

  • Samanin, R., Gumulka, W., Valzelli, L.: Reduced effect of morphine in midbrain raphe lesioned rats. Eur. J. Pharmacol. 10, 339–343 (1971)

    Google Scholar 

  • Scheel-Krüger, J.: Behavioural and biochemical comparison of amphetamine derivatives, cocaine, benztropine and tricyclic antidepressant drugs. Eur. J. Pharmacol. 18, 63–73 (1972)

    Google Scholar 

  • Tenen, S. S.: Antagonism of the analgesic effect of morphine and other drugs by p-chlorophenylalanine, a serotonin depletor. Psychopharmacologia (Berl.) 12, 278–285 (1968)

    Google Scholar 

  • Thornburg, J. E.: Drug-stimulated locomotor activity after selective inhibition of dopamine and norepinephrine synthesis in the brain. Fed. Proc. 31, 530 (1972)

    Google Scholar 

  • Toman, J. E.P., Swinyard, E. A., Goodman, L. S.: Properties of maximal seizures and their alterations by anticonvulsant drugs and other agents. J. Neuropsychiatry 9, 231–240 (1946)

    Google Scholar 

  • Trepanier, D. L., Shriver, K. L., Eble, J. N.: Aryl-substituted triazines with anti-depressant activity. J. Med. Chem. 12, 257–260 (1969)

    Google Scholar 

  • Tripathi, V. J., Ray, A. B., Dasgupta, B.: Chemical examination of Indian Nelumbo nucifera Gaertn. J. Inst. Chem. (India) 46, 200–202 (1974)

    Google Scholar 

  • Turner, R. A.: Screening methods in pharmacology, vol. 1, p. 21. New York: Academic 1965

    Google Scholar 

  • Van Rossum, J. M.: The significance of dopamine receptor blockade for mechanism of action of neuroleptic drugs. Arch. Int. Pharmacodyn. Ther. 160, 492–494 (1966)

    Google Scholar 

  • Wirth, W.: Versuche zur kombinierten Wirkung von Megaphen mit stark wirksamen Analgetics. Naunyn Schmiedebergs Arch. Exp. Pathol. Pharmakol. 222, 75–76 (1954)

    Google Scholar 

  • Zettler, F.: Erfahrungen mit der potenzierten Narkose und dem künstlichen Winterschlaf. Münch. Med. Wochenschr. 95, 1295–1296 (1953)

    Google Scholar 

  • Zettler, G.: Cataleptic state and hypothermia in mice caused by central cholinergic stimulation and antagonised by anticholinergic and antidepressant drugs. Int. J. Neuropharmacol. 7, 325–335 (1968)

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Bhattacharya, S.K., Bose, R., Ghosh, P. et al. Psychopharmacological studies on (-)-nuciferine and its Hofmann degradation product atherosperminine. Psychopharmacology 59, 29–33 (1978). https://doi.org/10.1007/BF00428026

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00428026

Key words

  • Aporphine alkaloid and derived arylethylamine
  • Nuciferine
  • Neuroleptic
  • Atherosperminine
  • Dopamine-receptor agonist/antagonist