A new type of β_1 -blocker, Bevantolol, also has Ca2+ blocking effects on CNS neuron

• Published in: Japanese Journal of Pharmacology 1994, Vol.64 (suppl.2), p.306-306
• Main Authors: Tomohiro Omura, Tadashi Kobayashi, Koichiro Nishioka, Norihisa Miyake, Norio Akaike
• Format: Article
• Language: Japanese
• ISSN: 0021-5198

Bevantotol, which has cardioselective β-adrenoceptor blocking activity, effectively reduces blood pressure in spontaneously hypertensive rats. The hypotensive profile is different from other β-blockers. In rat aorta ring preparation, it was demonstrated that bevantolol has additional calcium blocking action. Therefore, we studied the effect of bevantolol on rat CNS neurons by using a nystatin-perforated patch clamp technique under a voltage-clamp condition. As a preparation we used acutely dissociated rat ventro-medial hypothalamic (VMH) neurons. Bevantolol concentration-dependently inhibited the high-voltage-activated (HVA) calcium current elicited by step depolarization potential to more than -30mV from a holding potential of -50mV. The order of inhibitory potency against the HVA Ca current was bevantolol ＞ propranolol ＞ lavetalol ＞ atenolol. Bevantolol also concentration-dependently inhibited the low-voltage-activated (LVA) Ca current elicited by depolarizing step potential to more than -70mV from a holding potential of - -100mV. The IC_50 value of bevantolol against the LVA Ca current was 3x10^-6 M. The inhibitory effect on the LVA Ca current was augmented by increasing the stimulation frequency from 0.2Hz to 1Hz, indicating the presence of use-dependency. Bevantolol delayed the reactivation of the LVA Ca channel but had no effect on steady-state inactivation.