Nature 264, 76 - 79 (04 November 1976); doi:10.1038/264076a0

Anticholinergic and membrane activities of amantadine in neuromuscular transmission

WILLIAM L. NASTUK, PHILIP C. Su^* & PETER DOUBILET

Department of Physiology, College of Physicians and Surgeons, Columbia University, New York, New York 10032
^*Present address: Department of Medicine (Neurology), State University of New York at Stony Brook and Veterans Administration Hospital, Northport, New York 11768.

AMANTADINE hydrochloride (1-adamantanamine hydro-chloride, Symmetrel) is an antiviral agent which prevents certain viruses from penetrating cells¹⁻³. In addition, this drug is also effective in relieving clinical symptoms shown in parkinsonism⁴⁻⁸ this action of amantadine may depend on its capacity to increase the synthesis and release of dopamine from dopaminergic cells of the basal ganglia^9,10. To obtain additional evidence which might aid in explaining these remarkably diverse effects of amantadine, we used single-cell electrophysiological techniques to study its action on junctional and extrajunctional membranes. Our results show that amantadine, in clinically effective concentrations, rapidly inhibits neuromuscular transmission, and when applied over a longer period of time the drug also exerts a substantial effect on the conductile membranes of muscle fibres.

References

1.	Davies, W. L., et al., Science, 144, 862–863 (1964).
2.	Hoffman, C. E., Neumayer, E. M., Haff, R. F., and Goldsby, R. A., J. Bact., 90, 623–628 (1965).
3.	Maassab, H. F., and Cochran, K. W., Science, 145, 1443 (1964).
4.	Schwab, R. S., England, A. C., Jr., Poskanzer, D. C., and Young, R. R., J. Am. med. Ass., 208, 1168–1170 (1969).
5.	Parkes, J. D., Calver, D. M., Zilkha, K. J., and Knill-Jones, R. P., Lancet, i, 259–262 (1970).
6.	Millac, P., Hasan, I., Espir, M. L. E., and Slyfield, D. G., Lancet, i, 464 (1970).
7.	Appleton, D. B., Eadie, M. J., and Sutherland, J. M., Med. J. Aust., 2, 626–629 (1970).
8.	Dallos, V., Healthfield, K., Stone, P., and Allen, F. A. D., Br. med. J., 4, 24–26 (1970).
9.	Grelak, R. P., Clark, R., Stump, J. M., and Vernier, V. G., Science, 169, 203–204 (1970).
10.	Scatton, B., Cheramy, A., Besson, M. J., and Glowinski, J., Eur. J. Pharmac., 13 131–133 (1970).
11.	Nastuk, W. L., and Alving, B. O., Biochem. Pharmac., 1, 307–322 (1959).