Cardiovascular properties of LF 2.0254, a new potent vasoselective calcium channel blocker with a slow onset of action
Autor: | F. Roy, D. Pruneau, N L Brown |
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Rok vydání: | 1990 |
Předmět: |
Male
Dihydropyridines medicine.medical_specialty Nifedipine medicine.drug_class Guinea Pigs chemistry.chemical_element Calcium channel blocker In Vitro Techniques Calcium Plasma renin activity Muscle Smooth Vascular Calcium Chloride Norepinephrine Dogs medicine.artery Internal medicine medicine Animals Anesthesia Pharmacology (medical) Calcimycin Pharmacology Aorta Calcium Radioisotopes Calcium channel Hemodynamics Heart Calcium Channel Blockers Rats Endocrinology chemistry Decreased blood pressure Hypertension Circulatory system Potassium Female Rabbits Muscle Contraction medicine.drug |
Zdroj: | Fundamental & Clinical Pharmacology. 4:223-243 |
ISSN: | 1472-8206 0767-3981 |
Popis: | 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 CA2(+)-induced contractions of rabbit aorta with respective IC50 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 45Ca2(+)-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 microM only slightly decreased the contractile force and beating rate. In anesthetized open-thorax dogs, LF 2.0254 (1 to 100 micrograms/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 os) decreased blood pressure and concomitantly increased heart rate and plasma renin activity. It is concluded that LF 2.0254 differ markedly from nifedipine in its more gradual onset of action and greater selectivity for the vasculature with respect to the myocardium. |
Databáze: | OpenAIRE |
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