Effects of four drugs on 4-aminopyridine seizures: a comparison with their effects on HPNS.
The effects of two i.v. anesthetics, Saffan and methohexitone (MHX) and two N-methyl-D-aspartate receptor antagonists, MK-801 (Dizocilpine) and 2-aminophosphonoheptanoate (AP7), were tested for activity against the motor excitation (tremor, whole body jerks, and seizures) produced by the K+ channel blocker 4-aminopyridine (4-AP). Saffan increased the dose of 4-AP required for all three endpoints; MHX had no effect on tremor but reduced the 4-AP required to produce jerks and seizures. MK-801 also reduced the 4-AP dose required to produce jerking but did not affect tremor or seizures. In contrast, AP7 increased the amount of 4-AP required to produce all endpoints. The effects of these drugs on 4-AP-induced excitation are similar to their actions on hyperbaric excitation, reported by us previously, and suggest that blockade of K+ channels may contribute to the high pressure nervous syndrome.
Wardley-Smith
B
B
Division of Anaesthesia, Clinical Research Centre, Harrow, England.
Wann
K T
KT
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives*; D015761:4-Aminopyridine / Q000037:antagonists & inhibitors; D000596:Amino Acids / Q000494:pharmacology*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D006610:High Pressure Neurological Syndrome / Q000139:chemically induced*; D008297:Male; D008723:Methohexital / Q000494:pharmacology*; D011277:Pregnanediones / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D000596:Amino Acids; D000927:Anticonvulsants; D011277:Pregnanediones; D016291:Dizocilpine Maleate; D015763:2-Amino-5-phosphonovalerate; C006477:alphaxalone; D015761:4-Aminopyridine; D008723:Methohexital; C031231:2-amino-7-phosphonoheptanoic acid