A Comparison of the Pharmacological Properties of the Three Isomeric Aminopyridines

Fastier, F. N.; McDowall, MA

doi:10.1038/icb.1958.39

Cited by 40 publications

(14 citation statements)

References 2 publications

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“…As previously reported (Fragoso‐Veloz & Tapia, 1992; Világi et al., 2009), we have found here that systemic 4AP administration induces wet‐dog shakes, myoclonic jerks, fascicular twitching, forepaw tremor, chewing, myoclonus, and tonic–clonic seizures. The detailed mechanisms underlying such variety of symptoms remain unknown, although generalized fascicular twitching should presumably reflect enhanced neurotransmission at the neuromuscular junction (cf., Fastier & McDowall, 1958), as also suggested by the use of 4AP in the treatment of myasthenia gravis (Miller, 1979) and botulism (Ball et al., 1979). On the other hand, other symptoms may be linked to central effects induced by 4AP.…”

Section: Discussionmentioning

confidence: 84%

Temporal lobe epileptiform activity following systemic administration of 4‐aminopyridine in rats

et al. 2012

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SUMMARYPurpose: The K + channel blocker 4-aminopyridine (4AP) induces epileptiform synchronization in brain slices maintained in vitro without interfering with c-aminobutyric acid (GABA) A receptor-mediated inhibition and, actually, even enhancing it. The hypothesis that similar electrographic epileptiform patterns occur in vivo following systemic 4AP injection was tested here. Methods: Sprague-Dawley rats (n = 13) were implanted with bipolar electrodes aimed at the hippocampal CA3 region, entorhinal cortex, subiculum, dentate gyrus, and amygdala. They were then injected with a single dose of 4AP (4-5 mg/kg, i.p.), and video-monitoring/electroencephalography (EEG) recordings were performed. Key Findings: 4AP induced convulsive or nonconvulsive seizures in 12 of 13 rats, along with generalized fascicular twitching, wet-dog shakes, and myoclonic jerks. On EEG, we observed in 7 (58.3%) of 12 animals long-lasting interictal spikes from the subiculum before the occurrence of the first seizure. Once seizures had started, interictal spikes occurred in all areas with no fixed site of origin. Most seizures (41/60, 68.3%) were characterized by a lowvoltage fast-activity onset pattern and were convulsive (48/60, 80%). 4AP also induced highly rhythmic theta (6-11 Hz) oscillations in CA3 and entorhinal cortex before seizure occurrence. Significance: Our study shows that systemic 4AP administration in vivo can enhance theta oscillations and induce slow interictal spikes and low-voltage fast-onset seizures similar to those reported in brain slices. We propose that these effects may reflect, at least in part, enhanced GABA A receptor-mediated inhibition as reported in in vitro studies.

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Section: Discussionmentioning

confidence: 84%

Temporal lobe epileptiform activity following systemic administration of 4‐aminopyridine in rats

et al. 2012

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“…4-APYR was found to facilitate neuromuscular transmission (fastier and McDowall, 1958;Foldes et al, 1976;Bowman et aI., 1976), increase quantal content and antagonize the action of tubocurarine in nerve-skeletal muscle preparations (Lemeignan and Lechat, 1967;foIdes et aI., 1976). Lundh et al (1977) found that 4-APYR restores neuromuscular transmission both in vivo and in vitro in rats poisoned with Botulinus A toxin.…”

Section: Introductionmentioning

confidence: 95%

The effect of 4-aminopyridine on acetylcholine release

Vizi

Dijk

Foldes

1977

J. Neural Transmission

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The effect of 2-, and 4-aminopyridine (4-APYR) on the release mechanism of acetylcholine (ACh) from the nerve terminals of the Auerbach plexus-longitudinal muscle preparation of the guinea-pig ileum, suspended in eserinized Krebs' solution, was investigated. 2- and 4-APYR increased the release of ACh from the nerve terminals at rest and at both low and high frequency stimulation. The enhanced ACh release was found to be due to increased volley output. At lower frequency of stimulation, potentiation of ACh release was much higher than at higher rate of stimulation. 4-APYR was able to increase ACh release in the absence of [Ca2+]o. However, when a Ca-chelating agent, EDTA, was also added to the Ca-free Krebs' solution, 4-APYR was entirely ineffective. The depression of ACh release induced by Mg-excess was completely antagonized by 4-APYR. Tetrodotoxin (TTX) prevented augmentation of ACh release by 4-APYR. It is suggested that 4-APYR lowers the demand of nerve terminals for [Ca2+]o required for the excitation-secretion coupling process. The presence of a low concentration [Ca2+]o, however, is essential for the action of 4-APYR.

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“…These substances have now become indispensible tools for studying the behaviour of ionic channels in nerve and skeletal muscle. As yet there have been no reports of their effect on isolated preparations of vascular smooth muscle, although it has been shown that 2-, 3-and 4-aminopyridine (2-, 3-and 4-AP) have a pressor action in the cat and cause vasoconstriction in the perfused hindquarter of the rat (Fastier & McDowall, 1958), and 2-AP potentiates the vasoconstrictor action of adrenaline in the latter preparation (Fastier & Reid, 1948). The present results show that the aminopyridines, like TEA, cause a potentiation of vasoconstrictor responses to electrical stimulation, noradrenaline and histamine in the ear artery of the rabbit.…”

Section: Introductionmentioning

confidence: 99%

Potentiation of Vasoconstrictor Responses by 3‐ and 4‐aminopyridine

Glover

1978

British J Pharmacology

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1 In concentrations that are known to reduce potassium conductance in many excitable membranes, 3 and 4-aminopyridine (3-AP, 4-AP) potentiate vasoconstrictor responses of the isolated ear artery of the rabbit to noradrenaline and histamine. 2 3-and 4-AP have no effect on the responses of potassium-depolarized arteries to noradrenaline, histamine or calcium. 3 The results suggest that the aminopyridines have no direct effect on the contractile machinery or on pharmacomechanical coupling, but cause potentiation by influencing electrical events at the cell membrane. 4 4-AP causes a greater potentiation of the response to electrical stimulation than of the response to noradrenaline. This suggests that the aminopyridines may also cause an increase in the amount of noradrenaline released in response to sympathetic nerve stimulation.

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A Comparison of the Pharmacological Properties of the Three Isomeric Aminopyridines

Cited by 40 publications

References 2 publications

Temporal lobe epileptiform activity following systemic administration of 4‐aminopyridine in rats

Temporal lobe epileptiform activity following systemic administration of 4‐aminopyridine in rats

The effect of 4-aminopyridine on acetylcholine release

Potentiation of Vasoconstrictor Responses by 3‐ and 4‐aminopyridine

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