title: Suppression of calcium current in a snail neurone by eperisone and its analogues.
abstract: The effects of eperisone, tolperisone and isoperisone on the calcium current (ICa) were studied in an identified neurone of Achatina fulica under voltage clamping. At a holding voltage of -50 mV, these drugs inhibited ICa dose dependently without affecting activation time. Eperisone (IC50 = 0.348 mM) and isoperisone (0.226 mM) were significantly more effective than tolperisone (1.089 mM). Eperisone binds competitively with Ca2+ to the Ca2+ channels, based on its effects seen with various extracellular Ca2+ concentrations. The three drugs shifted the steady state inactivation curves in the hyperpolarizing direction. The mean dissociation constants for inactivated Ca2+ channels were calculated to be 0.070 mM (eperisone), 0.162 mM (tolperisone) and 0.014 mM (isoperisone). These values were much lower than their IC50 at Vh of -50 mV, which are reflected as the dissociation constants for resting Ca2+ channels. High frequency stimulation did not potentiate ICa suppression, suggesting that the drugs hardly bind to activated Ca2+ channels. These findings indicate that the selectivities of the Ca2+ channels to the drugs are in the order of their inactivated, resting and open states.
authors.affiliation: Department of Physiology, Gifu University School of Medicine, Japan.
authors.forename: P
authors.initials: P
authors.lastname: Novales-Li
authors.forename: X P
authors.initials: XP
authors.lastname: Sun
authors.forename: H
authors.initials: H
authors.lastname: Takeuchi
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects*; D055598:Chemical Phenomena; D002621:Chemistry; D004594:Electrophysiology; D005724:Ganglia / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008839:Microelectrodes; D009474:Neurons / Q000187:drug effects*; D011427:Propiophenones / Q000494:pharmacology*; D012908:Snails / Q000502:physiology*; D014049:Tolperisone / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D011427:Propiophenones; C030848:eperisone; C061812:isoperisone; D014049:Tolperisone