THE EFFECTS OF PIPEROXAN ON UPTAKE OF NORADRENALINE AND OVERFLOW OF TRANSMITTER IN THE ISOLATED BLOOD PERFUSED SPLEEN OF THE CAT

The competitive α‐adrenoceptor blocking agent, piperoxan, in concentrations up to 2 × 10⁻⁴m, produced large dose‐dependent increases in transmitter overflow from the isolated blood perfused spleen of the cat following nerve stimulation at 10 hertz. At concentrations greater than 2 × 10 ⁻⁴ m, piperoxan produced a rise in perfusion pressure, a contraction of the splenic capsule, and a marked dose‐dependent decrease in transmitter overflow. Phenoxybenzamine (10⁻⁴m) and desmethylimipramine (3 × 10⁻⁵m) produced further increases in transmitter overflow when added after piperoxan. Piperoxan (5.8 to 6.6 × 10⁻⁶m) had no effect on the recovery of ³H in the venous blood following the close arterial infusion or injection of [³H]‐(−)−noradrenaline, indicating that the drug does not inhibit uptake of the amine. Piperoxan produced dose‐dependent inhibition of responses of the splenic vasculature to close arterial injection of 1 μg of (—)‐noradrenaline but was much less effective at inhibiting responses to nerve stimulation. At 2 × 10 ⁻⁶m piperoxan produced a considerable reduction of the response to injected noradrenaline but potentiated the response to nerve stimulation. In isolated strips of cat splenic capsule, piperoxan produced a shift to the right of the dose‐response curve to noradrenaline with no change of the maximum response. There was no evidence of a postsynaptic sensitizing effect of the type observed in the rat vas deferens. 1978 British Pharmacological Society