The role of potassium channels in antihistamine analgesia

The effect of the administration of pertussis toxin as well as modulators o f different subtypes of K+ channels on the antinociception induced by the H -1-antihistamines pyrilamine, diphenhydramirie and promethazine was evaluat ed in the mouse hot plate test. Pretreatment with pertussis toxin (0.25 mu g/mouse i.c.v.) prevented pyrilamine, diphenhydramine and promethazine anti nociception. The K-ATP channel openers minoxidil and pinacidil potentiated the antinociception produced by the H-1-antihistamines whereas the K-ATP ch annel blocker gliquidone prevented the anti H-1-induced analgesia. The Ca2-gated K+ channel blocker apamin antagonized pyrilamine, diphenhydramine an d promethazine analgesia. Pretreatment with an antisense oligonucleotide (a ODN) to mKv1.1, a voltage-gated K+ channel, at the dose of 3.0 nmol/single i.c.v. injection, never modified the antinociception induced by the H-1-ant ihistamines in comparison with degenerate oligonucleotide (dODN)-treated mi ce. At the highest effective doses, none of the drugs used modified animals ' gross behaviour nor impaired motor coordination, as revealed by the rota rod test. The present data demonstrate that both K-ATP and Ca2+-gated K+ ch annels, contrary to voltage-gated K+ channel Kv1.1, represent an important step in the transduction mechanism underlying central antinociception induc ed by H-1-antihistamines. (C) 1999 Elsevier Science Ltd. All rights reserve d.