Suppression of calcium current in a snail neurone by eperisone and its analogues.
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.
Novales-Li
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P
Department of Physiology, Gifu University School of Medicine, Japan.
Sun
X P
XP
Takeuchi
H
H
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
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D011427:Propiophenones; C030848:eperisone; C061812:isoperisone; D014049:Tolperisone