Pharmacological profile of barnidipine: a single optical isomer dihydropyridine calcium antagonist.
This article reviews the pharmacological profile of the dihydropyridine calcium antagonist (CaA) barnidipine [(+)-(3'S,4S)-3-(1'-benzyl-3'-pyrrolidinyl)-methyl-2,6-dimethyl-4-(m-nit rophenyl)-1,4dihydropyridine-3,5-dicarboxylate x HCl]. The characteristics and potential advantages of its pharmacological selectivity are also outlined. Barnidipine is an L-type CaA with high affinity for [3H]nitrendipine binding sites (Ki = 0.21 nmol/l). Its pharmacological profile has been studied in a variety of isolated tissues and animal models, such as isolated coronary arteries (pig, dog, rat), aorta (guinea pig) and in hypertensive rats (spontaneously hypertensive, renal hypertensive, desoxycorticosterone acetate [DOCA]-salt). Barnidipine may be characterized as a highly potent drug with vasoselectivity and, accordingly, a lack of negative inotropic activity. The onset of its action in vivo is slow, and it does not elicit reflex tachycardia. Its long duration of action, due to its lipophilicity, means that satisfactory control of elevated blood pressure can be obtained with once-daily dosing. Another interesting feature of barnidipine is its stereoselectivity. As the barnidipine molecule contains two chiral centres, it can have four possible enantiomers. The active component in the capsules used clinically consists of the S,S form, which is the most potent and longest acting of the four enantiomers.
van Zwieten
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Department of Pharmacotherapy, Academic Medical Centre, University of Amsterdam, The Netherlands.
D000818:Animals; D002121:Calcium Channel Blockers / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D004095:Dihydropyridines / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D004285:Dogs; D006168:Guinea Pigs; D006973:Hypertension / Q000188:drug therapy*; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D011918:Rats, Inbred SHR; D013329:Structure-Activity Relationship
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; C050699:mepirodipine; C038806:1,4-dihydropyridine; D009543:Nifedipine