Sodium‐dependent inhibition by PN200‐110 enantiomers of nicotinic adrenal catecholamine release

Abstract

1 Dimethylphenylpiperazinium (DMPP) or high K concentrations evoke catecholamine release from perfused cat adrenal glands; in both cases the secretory response was significantly enhanced in the absence of Na. Tetrodotoxin did not modify the nicotinic secretory response. 2 The (+)-and (-)enantiomers of the dihydropyridine Ca channel blocker PN200-110 show a high degree of stereoselectivity in the inhibition of catecholamine secretion evoked by high K or by DMPP in the presence of Na, the (+)-enantiomer being 57 and 80 times more potent, respectively, than the (-)-enantiomer. Both, noradrenaline and adrenaline release were equally depressed by PN200-1 10.3 The IC50 values for (+)-and (-)-PN200-110 for blockade of the secretory response induced by K or DMPP in the presence of Na are in the same range. In the absence of Na, (-)-PN200-110 did not affect DMPP-evoked secretion; however, the (+ )-enantiomer partially inhibited it. 4 The results suggest that the physiological catecholamine release from chromaffin cells is preceded by Na entry through the nicotinic receptor-associated ionophore; this causes cell depolarization, opening of voltage-dependent, dihydropyridine-sensitive Ca channels, and Ca entry into the cell. In the absence of Na, additional Ca influx through an alternative pathway (the nicotinic cholinoceptor ionophore?) might also activate secretion.

Capillary electrophoresis method for the determination of isradipine enantiomers: Stability studies and pharmaceutical formulation analysis

“…Hof et al [4] showed a large difference in pharmacological effects of enantiomers, where (1)-(S)-IRD presented inhibition of depolarization-induced contraction of rabbit aorta in vitro 160 times greater than (À)-(R)-IRD, and with in vivo studies, this difference was found 30-and 300-fold, with respect to subendocardial coronary blood flow and blood pressure, respectively. Other differences in activity have been reported [5,6]. Since the pharmacological effects of the enantiomers can be different, there is a need for the development of enantioselective methods.…”

Aplicações da eletroforese capilar na análise do biomarcadir alfa-1 glicoproteína ácida, no controle de qualidade do biofármaco interferon alfa 2a e na avaliação da estabilidade enantiosseletiva do fármaco isradipina

“…Uma vez que os efeitos farmacológicos dos enantiômeros da IRD podem ser diferentes (CARDENAS et al, 1988;HANDROCK et al, 1999), há uma necessidade do desenvolvimento de métodos enantiosseletivos. Diversos métodos, utilizando a cromatografia quiral, tem sido apresentados para a análise enantiosseletiva da IRD.…”