I. Pharmacological studies with derivatives of 2-aminotetralin, benzhydro[f]quinoline and clonidine suggest a pharmacological identity between peripheral and central alpha-2 adrenoceptors.

A series of hydroxy 2-aminotetralins, benzhydro[f]quinolines and clonidine were used to determine whether a pharmacological similarity could be demonstrated between presynaptic alpha adrenoceptors which modulate autonomic transmission in the guinea pig. Compounds were assayed on isolated field stimulated guinea-pig ilea (GPI) to determine their inhibitory activities on cholinergic transmission. Inhibition of noradrenergic transmission was determined by assaying compounds on isolated field stimulated guinea-pig atria. 2-Aminotetralins, benzhydro[f]quinolines and clonidine impaired cholinergic and noradrenergic transmission by interacting with presynaptic alpha-2 adrenoceptors. A correlation (r = 0.95; P less than .05) was demonstrated between the activity of a compound on the GPI and guinea-pig atria. IC50 values obtained on GPI were correlated with previously reported IC50 values obtained for binding [3H]clonidine sites in homogenates of calf frontal cortex. A significant correlation was demonstrated (r = 0.99; P less than .05). These data suggest that alpha-2 adrenoceptors localized on guinea-pig atria and GPI are pharmacologically similar. In addition, a similar structure activity relationship was demonstrated for presynaptic alpha-2 adrenoceptors on GPI and binding sites labeled by [3H]clonidine in the calf frontal cortex.