Clinical efficacy of efonidipine hydrochloride, a T-type calcium channel inhibitor, on sympathetic activities.
Dihydropyridine Ca antagonists cause reflex tachycardia related to their hypotensive effects. Efonidipine hydrochloride has inhibitory effects on T-type Ca channels, even as it inhibits reflex tachycardia. In the present study, the influence of efonidipine hydrochloride on heart rate and autonomic nervous function was investigated. Using an electrocardiogram and a tonometric blood pressure measurement, autonomic nervous activity was evaluated using spectral analysis of heart rate/systolic blood pressure variability. Three protocols were used: (1) a single dose of efonidipine hydrochloride was administered orally to healthy subjects with resting heart rate values of 75 beats/min or more (high-HR group) and to healthy subjects with resting heart rate values less than 75 beats/min (low-HR group); (2) efonidipine hydrochloride was newly administered to untreated patients with essential hypertension, and autonomic nervous activity was investigated after a 4-week treatment period; and (3) patients with high heart rate values (>/=75 beats/min) who had been treated with a dihydropyridine L-type Ca channel inhibitor for 1 month or more were switched to efonidipine hydrochloride and any changes in autonomic nervous activity were investigated. In all protocols, administration of efonidipine hydrochloride decreased the heart rate in patients with a high heart rate, reduced sympathetic nervous activity, and enhanced parasympathetic nervous activity. In addition, myocardial scintigraphy with (123)I-metaiodobenzylguanidine showed significant improvement in the washout rate and H/M ratio of patients who were switched from other dihydropyridine Ca antagonists to efonidipine hydrochloride. Efonidipine hydrochloride inhibits increases in heart rate and has effects on the autonomic nervous system. It may be useful for treating hypertension and angina pectoris, and may also have a cardiac protective function.
Harada
Kenji
K
Department of Digestive and Cardiovascular Medicine, University of Tokushima, Japan.
Nomura
Masahiro
M
Nishikado
Akiyoshi
A
Uehara
Kouzoh
K
Nakaya
Yutaka
Y
Ito
Susumu
S
D019797:3-Iodobenzylguanidine; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D004095:Dihydropyridines / Q000008:administration & dosage / Q000494:pharmacology*; D004562:Electrocardiography; D005260:Female; D006321:Heart / Q000000981:diagnostic imaging / Q000187:drug effects / Q000294:innervation; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy; D007457:Iodine Radioisotopes; D008297:Male; D009596:Nitrophenols / Q000008:administration & dosage / Q000494:pharmacology*; D009943:Organophosphorus Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D011877:Radionuclide Imaging; D013057:Spectrum Analysis; D013564:Sympathetic Nervous System / Q000187:drug effects*; D013610:Tachycardia / Q000139:chemically induced / Q000000981:diagnostic imaging; D016896:Treatment Outcome
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D007457:Iodine Radioisotopes; D009596:Nitrophenols; D009943:Organophosphorus Compounds; D019797:3-Iodobenzylguanidine; C066425:efonidipine