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The experimental compounds St-1913, St-1966 and St-1967 in which the bridging nitrogen atom, as found in clonidine, has been replaced by a methylene (--CH2--) function, an oxygen or a sulphur atom, respectively, have been investigated with respect to their acute hypotensive effects in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.

Hypotensive and bradycardic effects of classical alpha-sympathomimetic drugs upon intravenous administration to pentobarbitone-anaesthetized rats.

The effects of the classical alpha-sympathomimetic drugs naphazoline, tramazoline, xylometazoline, tetryzoline and oxymetazoline on blood pressure and heart rate of pentobarbitone-anaesthetized (75 mg/kg; i.p.) normotensive rats were studied following intravenous injections. With the aid of this experimental animal model a dose dependent decrease in mean arterial pressure and heart rate could be established for these agents, oxymetazoline excepted, for which only the bradycardia could be quantified. It is suggested that central alpha-adrenoceptors are involved in the mechanism of this cardiovascular inhibition in view of the most specific alpha-adrenoceptor-stimulating properties of these ddrugs. Additionally, the results indicate that the use of pentobarbitone as the anaesthetic enhances the hypotensive action of these agents, so that their pronounced peripheral vasopressive response can be overcome.