Analysis of the action of 4-aminopyridine during repetitive stimulation at the neuromuscular junction

4‐aminopyridine Blockade of Neuronal Depressant Responses to Adenosine Triphosphate

“…4-Aminopyridine (4-AP) is a compound widely used experimentally to block membrane potassium channels (Meves & Pichon, 1977; Ulbricht, 1977;Hosli, Andres & Hosli, 1979) and, probably as a result of that action, to increase transmitter release from nerve terminals (Molgo, Lemeignan & Lechat, 1979;Tokunaga, Sandri & Akert, 1979). Although 4-AP would not be expected to block those potassium channels activated by transmitter action (Llinas, Walton & Bohr, 1976;Jankowska, Lundberg, Rudomin & Sykova, 1977;Molgo, Lemeignan & Lechat, 1977;Lundh, 1978;McGeer, Eccles & McGeer, 1978;Hosli et al, 1979) the structural formulae of 4-AP and adenine are sufficiently similar that it was decided to examine the effects of 4-AP on central neurones.…”

4-Aminopyridine Hydrochloride (Pymadin)

“…4-Aminopyridine does not antagonise neuromuscular block produced by the depolarising agents, decamethonium or suxamethonium (LEMEIGNAN and LECHAT 1967;FOLDES et al 1976b). The compound is devoid of anticholinesterase activity in any dose that might be administered in vivo (SHAW and BENTLEY 1953;LEMEIGNAN and LECHAT 1967), and in fact a wide range of studies involving mechanical recording, electrophysiological analysis, collection and assay of acetylcholine, and electron microscope studies have demonstrated that the facilitatory action of 4-aminopyridine, and derivatives of it, on neuromuscular transmission is the result of a prejunctional effect on the nerve endings through which the evoked release of acetylcholine is increased (LEMEIG-NAN and LECHAT 1967;SOBEK et al 1968;MOLGO et al 1975MOLGO et al , 1977MOLGO et al , 1979BOWMAN et al 1976;HARVEY and MARSHALL 1977 a, b, c;LUNDH and THESLEFF 1977;HEUSER 1977;ILLES and THESLEFF 1978;LUNDH 1978a;JACOBS and BURLEY 1978;MARSHALL 1978, 1980;KATZ and MILEDI 1979;HEUSER et al 1979;THESLEFF 1980;KIM et al 1980 a;MAENO 1980;MOLGO 1982).…”

“…When trains of stimuli at frequencies of 4-50 Hz were applied to a partially curari sed frog nerve-muscle preparation only the first one or two end-plate potentials in each train were enhanced by 4-aminopyridine. The subsequent impulses in each train evoked rapidly diminishing responses (LUNDH 1978 a;ILLES and THESLEFF 1978;MOLGO et al 1979;HEUSER et al 1979), presumably because the demand by the facilitated release process exceeds the supply that can be met by mobilisation. BOWMAN et al (Chap.…”

“…Part of this figure has been published elsewhere (AGOsToN et al 1982) 4-Aminopyridine Hydrochloride (Pymadin) 685 LEFF 1980;MOLGO 1982;GLOVER 1982). Analysis of the junctional events indicates that 4-aminopyridine increases the average number of quanta m released in response to a nerve impulse by increasing the binomial parameter n, but without affecting the mean probability p of release (LUNDH 1979;MOLGO et al 1979). It has been suggested that the physical counterpart of n may be the number of functional transmitter release sites at the nerve terminal, and morphological evidence supports this possibility.…”

Synaptic facilitatory and depressant actions of 3,4-diaminopyridine: Correlation with anticurare properties.

“…Amplitudes of post junctional potentials are therefore enhanced (2,3), and repetitive postjunctional responses to a single prejunctional stimulus can also be generated (4,5). Not unexpectedly, the aminopyridines exhibit anticurare efficacy in animals (1-7), and man (8)(9)(10) and have antimyasthenic properties as well (11 ).…”