Pharmacodynamic effects of a 2-piperazinotetralin (P-11)--combined alpha- and beta-adrenoceptor blocking drug with hypotensive action.

The piperazinotetralin derivative P-11 at hypotensive doses of 0.25 to 1.00 mg/kg i.v. reduced the pressor effects of exogenous noradrenaline (10 micrograms/kg i.v.) in reserpine-pretreated rats, but was ineffective in nonreserpinized normotensive urethane-anesthetized rats. P-11 (0.25 to 1.00 mg/kg i.v.) decreased the positive chronotropic effects of isoprenaline (0.2 micrograms/kg i.v.), but potentiated the isoprenaline-induced hypotension in reserpine-pretreated rats. P-11 (10(-7) to 10(-5)M) did not modify the concentration-effect curves for isoprenaline in carbachol-contracted guinea-pig tracheal strips. The pD2 value of isoprenaline was 5.94 before and 6.35 after P-11. The combined alpha1-postsynaptic antagonist/beta1-blocking activity of this compound is discussed.