Premium
Cardiovascular properties of LF 2.0254, a new potent vasoselective calcium channel blocker with a slow onset of action
Author(s) -
Pruneau D.,
Roy F.,
Brown NL
Publication year - 1990
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/j.1472-8206.1990.tb00490.x
Subject(s) - nifedipine , dihydropyridine , calcium channel blocker , medicine , blood pressure , chemistry , cardiology , calcium
Summary— The effects of LF 2.0254, a new 1,4‐dihydropyridine derivative, were studied in rabbit aorta stimulated by various contractile agents and in isolated guinea pig atria. LF 2.0254 inhibited in a time‐dependent fashion K+‐ and CA 2+ ‐induced contractions of rabbit aorta with respective IC 50 of 2.7 nM and 1.7 nM. An action of LF 2.0254 at the voltage operated calcium channel was consistent with the finding that LF 2.0254 antagonized 45 Ca 2+ ‐uptake induced by depolarisation of smooth muscle, and since contractile responses evoked by (‐) norepinephrine and the calcium ionophore A23187 were insensitive to the drug. In isolated paced left atria and spontaneously beating right atria of guinea pig, LF 2.0254 added for 60 min at 1 μM only slightly decreased the contractile force and beating rate. In anesthetized open‐thorax dogs, LF 2.0254 (1 to 100 μg/kg, iv) dose‐dependently lowered systemic blood pressure and increased cardiac output with a slower onset of action than nifedipine. LF 2.0254 and nifedipine decreased total peripheral, coronary, femoral and vertebral resistance. In marked contrast to nifedipine, LF 2.0254 induced only a slight decrease in left ventricular dP/dt. In conscious hypertensive dogs LF 2.0254 (0.1 and 0.3 mg/kg per or ) decreased blood pressure and concomitantly increased heart rate and plasma renin activity. It is concluded that LF 2.0254 differs markedly from nifedipine in its more gradual onset of action and greater selectivity for the vasculature with respect to the myocardium.