The hypotensive mechanisms of pindolol in anesthetized and conscious rats were investigated. Pindolol caused a fall in blood pressure in anesthetized, conscious and spinal rats, though in conscious rats a higher dose of the drug was required to produce such a response. This hypotension with pindolol in anesthetized and conscious rats was markedly inhibited by pretreatment with the drug itself or other beta-adrenoceptor blocking drugs. A similar phenomenon also occurred when isoproterenol was injected intravenously in anesthetized and conscious rats. The relationship between the hypotensive actions of four beta-adrenoceptor blocking drugs in anesthetized rats and their intrinsic beta-sympathomimetic actions in isolated catecholamine-depleted tracheal preparations was determined. Order of hypotensive potencies was the same as that of their intrinsic beta-sympathomimetic action, namely, pindolol greater than carteolol greater than bufetolol in equilibrium propranolol (p less than 0.05). These results suggest that the hypotension with pindolol is mediated through a decrease in the peripheral vascular resistance due to an intrinsic beta-sympathomimetic action of the drug.

Intracellular localization of histamine receptors in small intestinal smooth muscle of the cat was studied by investigating distribution of marker enzymes in the receptor rich fraction. Distribution of membrane markers coincided with that of the radiochemically labeled receptor fraction. Membrane fraction was further purified and it was concluded that the histamine receptor rich fraction is mainly composed of cell membrane. The chemical composition of the fraction lent support to this conclusion.

The structure-activity relationship between the hypotensive and some general pharmacological effects of aminoguanidine derivatives was investigated and the following results were obtained.1) A moderate length of the intermediate chain between the benzene ring and the aminoguanidino group of the test compounds was required to obtain a much longer hypotension, and the introduction of one methylene group gave the optimum activity.2) Among the test compounds, the benzyl- and benzylidene-hydrazino-3, 4, 5, 6-tetra-hydropyrimidines (BHTP) showed a relatively mild and slowly acting hypotensive effect with a long duration.3) Substitution of 2- and 6-positions in the benzene ring of BHTP with dichloro groups gave a marked hypotensive and some strong general pharmacological actions and, in particular, the anti-form isomer of 2-(2, 6-dichlorobenzylidenehydrazino)-3, 4, 5, 6-tetra-hydropyrimidines (VA) showed the most marked action.4) VA aid not show an α-sympathomimetic action as clonidine, etc., did.5) VA had an inhibitory action as potent as guanethidine on the contractions of the isolated guinea-pig hypogastric nerve-vas deferens induced by electrical stimulations.6) VA inhibited the contractile force of the isolated guinea-pig atria and decreased the heart rate of the isolated rat atria.7) VA had an inhibitory revolution mortor activity in mice, a taming effect in rats, and a sedative and hypnotic action in cats.8) A toxic dose of VA showed clonic convulsion, tremor, and hind leg ataxia, but did not show group toxicity and biting behavior as did clonidine in grouping mice.