Central hypotensive action of bridge analogues of clonidine

The experimental compounds St-1913, St-1966 and St-1967 in which the bridging nitrogen atom, as found in clonidine, has been replaced by a methylene (--CH2--) function, an oxygen or a sulphur atom, respectively, have been investigated with respect to their acute hypotensive effects in anaesthetized cats. Attention was paid to a possible contribution of the central nervous system to the hypotensive action of the drugs by means of vertebral arterial infusions. Although less active than clonidine, St-1913 and St-1967 are centrally acting hypotensive drugs. Central alpha-adrenoceptors are presumably involved in a similar manner as in the mechanism of clonidine. The hypotensive potency of St-1966 was much lower compared to the aforementioned drugs. A central origin for its depressor effects could be established. However, central alpha-adrenoceptors probably do not participate. In spite of its structural similarity with clonidine the mechanism of action of St-1966 appears to be different.