Histamine H1 antagonists block M-currents in dissociated rat cortical neurons.
We investigated the effects of histamine H1 antagonists on acutely dissociated neurons from the rat cortex using the patch-clamp technique. First-generation antihistamines, such as pyrilamine, d-chlorpheniramine, diphenhydramine, and ketotifen, suppressed M-currents in a concentration-dependent manner with respective half-inhibition concentrations (C50) of 35.9, 48.5, 34.8, and 47.8 microM at a holding potential of -26.5 mV. Astemizole, a second-generation antihistamine, inhibited M-currents with a C50 of 18.1 microM, but cetirizine did not do so, up to a concentration of 300 microM. Neither ranitidine nor cimetidine, both H2 antagonists, suppressed M-currents. The C50 of pyrilamine significantly decreased with membrane hyperpolarization, suggesting that it acts directly on M channel pores. The inhibition of M channels may be involved in the neurotoxic effects of histamine H1 antagonist overdose.
Sato
Ikuko
I
Department of Pediatrics, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.
Munakata
Mitsutoshi
M
Iinuma
Kazuie
K
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology; D007473:Ion Channels / Q000187:drug effects* / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013779:Tetrodotoxin / Q000494:pharmacology
D006634:Histamine H1 Antagonists; D007211:Indoles; D007473:Ion Channels; D026902:Potassium Channel Blockers; D011725:Pyridines; D013779:Tetrodotoxin; C061017:linopirdine