Summary
The effects of 2-, 3-, and 4-aminopyridines were investigated on the isolated chick biventer cervicis nerve-muscle preparation and on nerve-free cell cultures of embryonic chick skeletal muscle. All 3 compounds reversed tubocurarine blockade and augmented twitch height in indirectly stimulated biventer cervicis preparations. 4-Aminopyridine was approximately 10 times more potent than 2-, or 3-aminopyridine. Twitch augmentation was also seen in directly stimulated preparations but to a much lesser extent. The compounds did not have significant anticholinesterase activity, nor did they have any depolarizing activity when tested on nerve-free cultured muscle fibres. At high concentrations the aminopyridines produced a maintained contracture in the biventer preparations which was enhanced by neostigmine and inhibited by tubocurarine. It is suggested that the aminopyridines facilitate neuromuscular transmission by increasing acetylcholine release in response to nerve stimulation, and that the compounds can also increase spontaneous transmitter release.
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Benoit, P. R., Mambrini, J.: Modification of transmitter release by ions which prolong the presynaptic action potential. J. Physiol. (Lond.) 210, 681–695 (1970)
Bowman, W. C., Harvey, A. L., Marshall, I. G.: Facilitatory actions of aminopyridines on neuromuscular transmission. J. Pharm. Pharmacol. 28, Suppl., 79P (1976)
Crawford, A. C., Fettiplace, R.: A method for altering the intracellular calcium concentration. J. Physiol. (Lond.) 217, 20–21P (1971)
Dingemanse, E., Wibaut, J. P.: Zur Pharmakologie von einigen Pyridylpyrrolen und einigen Abkömmlingen des α-Aminopyridins. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak. 132, 365–381 (1928)
Fastier, F. N., McDowall, M. A.: A comparison of the pharmacological properties of the three isomeric aminopyridines. Aust. J. exp. Biol. med. Sci. 36, 365–372 (1958)
Ginsborg, B. L., Warriner, J.: The isolated chick biventer cervicis nerve-muscle preparation. Brit. J. Pharmacol. 15, 410–411 (1960)
Harvey, A. L., Dryden, W. F.: Studies on the pharmacology of skeletal muscle in culture: specificity of receptor. Europ. J. Pharmacol. 28, 125–130 (1974)
Hauschka, S., Konigsberg, I. R.: The influence of collagen on the development of muscle clones. Proc. nat. Acad. Sci. (Wash.) 55, 119–126 (1966)
Hille, B.: The selective inhibition of delayed potassium currents in nerve by tetraethylammonium ion. J. gen. Physiol. 50, 1287–1302 (1967)
Hue, B., Pelhate, M., Chanelet, J.: Effets de la 4-aminopyridine (4-AP) sur l'activité de la fibre nerveuse géante isolée d'insecte (Periplanta americana). J. Physiol (Paris) 67, 346A (1973)
Johns, A., Golko, D. S., Lauzon, P. A., Paton, D. M.: The potentiating effects of 4-aminopyridine on adrenergic transmission in the rabbit vas deferens. Europ. J. Pharmacol. 38, 71–78 (1976)
Konigsberg, I. R., McElvain, N., Tootle, M., Herrman, H.: The dissociability of deoxyribonucleic acid synthesis from the development of multinuclearity of muscle cells in culture. J. biophys. biochem. Cytol. 8, 333–343 (1960)
Krebs, H. A., Henseleit, K.: Untersuchungen über die Hamstoffbildung im Tierkörper. Hoppe-Seylers Z. physiol. Chem. 210, 33–66 (1932)
Lemeignan, M., Lechat, P.: Sur l'action anticurare des aminopyridines. C. R. Acad. Sci. (Paris) (D) 264, 169–172 (1967)
Lemeignan, M., Chanelet, J., Saade, N. E.: Etude de l'action d'un convulsivant spécial (la 4-aminopyridine) sur les nerfs de vertébrés. C.R. Soc. Biol. (Paris) 163 359–365 (1969)
Meves, H., Pichon, Y.: Effects of 4-aminopyridine on the current in internally perfused giant axons of the squid. J. Physiol. (Lond.) 251, 60–62P (1975)
Miledi, R., Thies, R.: Tetanic and post-tetanic rise in frequency of miniature end-plate potentials in low-calcium solutions. J. Physiol. (Lond.) 212, 245–257 (1971)
Pelhate, M., Pichon, Y.: Selective inhibition of potassium current in the giant axon of the cockroach. J. Physiol. (Lond.) 242, 90–91P (1974)
Pelhate, M., Hue, B., Chanelet, J.: Effets de la 4-amino-pyridine sur le système nerveaux d'un insecte: la blatte (Periplanta americana). C. R. Soc. Biol. (Paris) 166, 1598–1605 (1972)
Schauf, C. L., Colton, C. A., Colton, J. S., Davis, F. A.: Aminopyridines and sparteine as inhibitors of membrane potassium conductance: Effects on Myxicola giant axons and the lobster neuromuscular junction. J. Pharmacol. exp. Ther. 197, 414–425 (1976)
Tamiya, N., Arai, H.: Studies on sea snake venoms. Biochem. J. 99, 624–630 (1966)
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Bowman, W.C., Harvey, A.L. & Marshall, I.G. The actions of aminopyridines on avian muscle. Naunyn-Schmiedeberg's Arch. Pharmacol. 297, 99–103 (1977). https://doi.org/10.1007/BF00508816
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DOI: https://doi.org/10.1007/BF00508816