ANTAGONISM TO NORADRENALINE-INDUCED LETHALITY IN RATS IS RELATED TO AFFINITY FOR THE ALPHA(1A)-ADRENOCEPTOR SUBTYPE

The potency of several al-adrenoceptor antagonists in preventing the n oradrenaline-induced lethality in conscious rats, their binding affini ty for the native alpha(1A)- and alpha(1B)-adrenoceptors, the recombin ant animal alpha(1a)-, alpha(1b)- and alpha(1d)-adrenoceptor subtypes, as well as their functional affinity for the alpha 1L-adrenoceptor su btype were evaluated. The potency of the tested compounds as antagonis ts of noradrenaline-induced lethality was correlated with the affinity for the alpha(1A)- (and alpha(1a)-) adrenoceptor subtype, but not wit h the affinity for the other subtypes. On the contrary, the hypotensiv e effects of the compounds, assessed in anesthetized rats, were not cl early related with the affinity for any of the alpha(1)-subtypes. Thes e results suggest that the alpha(1A)-subtype plays a determining role in preventing lethality induced by noradrenaline in the rats, and that this activity is unrelated to the hypotensive effect of the compounds , which cannot be clearly correlated with affinity for a particular al pha(1)-adrenoceptor subtype.