Article date: August 1999
By: André S Pupo, Daniela L C Cavenaghi, Marcelo Campos, Paola de Lucena Morais, Neide H Jurkiewicz, Aron Jurkiewicz, in Volume 127, Issue 8, pages 1832-1836
The actions of the α1‐adrenoceptor antagonist indoramin have been examined against the contractions induced by noradrenaline in the rat vas deferens and aorta taking into account a putative neuronal uptake blocking activity of this antagonist which could result in self‐cancelling actions.
Indoramin behaved as a simple competitive antagonist of the contractions induced by noradrenaline in the vas deferens and aorta yielding pA2 values of 7.38±0.05 (slope=0.98±0.03) and 6.78±0.14 (slope=1.08±0.06), respectively.
When the experiments were repeated in the presence of cocaine (6 μM) the potency (pA2) of indoramin in antagonizing the contractions of the vas deferens to noradrenaline was increased to 8.72±0.07 (slope=1.10±0.05) while its potency remained unchanged in the aorta (pA2=6.69±0.12; slope=1.04±0.05).
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; slope=1.09±0.06).
It is suggested that indoramin blocks α1‐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 pKB values.
The actions of the α1‐adrenoceptor antagonist indoramin have been examined against the contractions induced by noradrenaline in the rat vas deferens and aorta taking into account a putative neuronal uptake blocking activity of this antagonist which could result in self‐cancelling actions.
Indoramin behaved as a simple competitive antagonist of the contractions induced by noradrenaline in the vas deferens and aorta yielding pA2 values of 7.38±0.05 (slope=0.98±0.03) and 6.78±0.14 (slope=1.08±0.06), respectively.
When the experiments were repeated in the presence of cocaine (6 μM) the potency (pA2) of indoramin in antagonizing the contractions of the vas deferens to noradrenaline was increased to 8.72±0.07 (slope=1.10±0.05) while its potency remained unchanged in the aorta (pA2=6.69±0.12; slope=1.04±0.05).
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; slope=1.09±0.06).
It is suggested that indoramin blocks α1‐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 pKB values.
British Journal of Pharmacology (1999) 127, 1832–1836; doi:10.1038/sj.bjp.0702735
DOI: 10.1038/sj.bjp.0702735
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