Antiaccelerator and decelerator activity of eleven phenothiazine derivatives.

Eleven N-substituted phenothiazine derivatives were studied for their antiaccelerator and decelerator activities on the dog heart. The antiaccelerator activity was determined in heart-lung preparation in dogs. Taking into consideration the percentage inhibition of cardio-acceleration produced by continuous infusion of 3 mug/min of adrenaline, all the drugs except chlorpromazine and 10-butyl-phenothiazine in two experiments caused more than 50 percent inhibition. 10-Propylphenothiazine induced maximum inhibitory effect, i.e. 90.1 percent in a total dose of 20 mg. Two types of effects were observed upon impulse generation in the sinus node. Acceleration was produced by chlorpromazine, 10-cyclopentyl-phenothiazine, prothipendyl, and thiazinamium, which was very short-lived, whereas other drugs produced deceleration. The correlation between antiaccelerator and decelerator properties is rather a close one.