Increased vascular selectivity and prolonged pharmacological efficacy of the L-type Ca2+ channel antagonist lercanidipine in human cardiovascular tissue.
1. The present study investigates the vasoselectivity of lercanidipine (LER), a 1,4-dihydropyridine calcium channel blocker, compared with amlodipine (AML) and nifedipine (NIF) in human cardiovascular tissue. Experiments were performed either in human left ventricular failing myocardium (orthotopic heart transplants) or in isolated right atrial trabeculae and isolated vessel preparations of arteria mammaria obtained from patients undergoing aortocoronary bypass operation. 2. The obtained rank order for the L-type Ca2+ channel affinity in human tissue was LER > NIF >or= AML. Lercanidipine had the lowest negative inotropic efficacy (1 micromol/L LER: 60.3% basal < AML: 79.1% basal < NIF: 92.4 basal) and potency (IC50 NIF: 3.5 nmol/L < AML: 48 nmol/L < Ler: 127 nmol/L) in right atrial trabeculae. 3. The vasorelaxant potency of LER (IC50 0.5 nmol/L) and AML (IC50 0.8 nmol/L) was similar and significantly increased compared with that of NIF (IC50 5.9 nmol/L) in arteria mammaria preparations of the very same patients. 4. The following rank order was obtained for vasoselectivity: LER (260) < AML (60) < NIF (0.6). 5. The pharmacological effects of LER and AML were still present 2 h after drug washout. 3. Lercanidipine is characterized by a high vasoselectivity and a prolonged interaction with the L-type calcium channel in human cardiovascular tissue This may be advantageous, especially in the treatment of patients with arterial hypertension.
Brixius
Klara
K
Laboratory of Muscle Research and Molecular Cardiology, Department of Internal Medicine III, University of Cologne, Cologne, Germany.
Gross
Thomas
T
Tossios
Paschalios
P
Geissler
Hans-Joachim
HJ
Mehlhorn
Uwe
U
Schwinger
Robert H G
RH
Hekmat
Khosro
K
D000293:Adolescent; D000328:Adult; D000368:Aged; D017311:Amlodipine / Q000494:pharmacology; D001667:Binding, Competitive; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000187:drug effects; D004095:Dihydropyridines / Q000494:pharmacology*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008323:Mammary Arteries / Q000187:drug effects; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology; D011485:Protein Binding; D013268:Stimulation, Chemical; D014664:Vasodilation / Q000187:drug effects*
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D004095:Dihydropyridines; D017311:Amlodipine; D009543:Nifedipine; C060343:lercanidipine