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.