Competitive antagonism associated with blockade of neuronal uptake: effects of indoramine in rat vas deferens and aorta

COMPETITIVE ANTAGONISM ASSOCIATED WITH BLOCKADE OF NEURONAL UPTAKE: EFFECTS OF INDORAMINE IN RAT VAS DEFERENS AND AORTA

ANDRÉ S. PUPO1, DANIELA L.C. CAVENAGHI1, MARCELO CAMPO1, PAOLA DE LUCENA MORAIS1, NEIDE H. JURKIEWICZ2 and ARON JURKIEWICZ2

1Department of Pharmacology, Instituto de Biociências, UNESP, 18600-000 Botucatu, Brazil

2Department of Pharmacology, UNIFESP, Escola Paulista de Medicina, 04023-900 São Paulo, Brazil.

The a1-adrenoceptor antagonist indoramin was used in the rat vas deferens and aorta, against contractions induced by noradrenaline. Indoramin behaved as a competitive antagonist yielding pA2 values of 7.38 ± 0.05 in rat vas deferens and 6.78 ± 0.14 in aorta. In the presence of cocaine (6mM), the potency (pA2) of indoramin in antagonizing the contractions of the vas deferens to noradrenaline was increased to 8.72 ± 0.07 while its potency remained pratically unchanged in the aorta (6.69 ± 0.12). In denervated vas deferens, indoramin antagonized the contractions to noradrenaline with a potency similar to that found in the presence of cocaine (8.79 ± 0.07). It is suggested that indoramin blocks simultaneously a1-adrenoceptors and neuronal uptake in rat vas deferens, resulting in Schild plots with slopes not different from unity even in the absence of selective inhibition of neuronal uptake. As a major consequence of this double mechanism of action, the pA2 values for this antagonist are underestimated when calculated in situations where the neuronal uptake is active, yielding spurious pAB values.

— ( September 14, 1999 ) .

Publication Dates

  • Publication in this collection
    07 Aug 2000
  • Date of issue
    Mar 2000
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