RO-5-4864 HAS A NEGATIVE INOTROPIC EFFECT ON HUMAN ATRIAL MUSCLE STRIPS THAT IS NOT ANTAGONIZED BY PK 11195

The effects of Ro 5-4864, a peripheral benzodiazepine receptor agonist (9 X 10(-6) M and 9 x 10(-5) M) and of PK 11195, a peripheral benzodi azepine receptor antagonist (3 X 10(-6) M and 3 x 10(-5) M), alone or together, on contraction parameters of human atrial muscle strips were studied. Atrial muscle strips were obtained from patients undergoing cardiac surgery. The strips were suspended in Krebs-Henseleit solution at 36.8 +/- 0.2 degrees C, connected to an isometric force transducer and then stimulated at 15 V above threshold and paced at 1.5 Hz. Ro 5 -4864 at its higher concentration, alone or mixed with PK 11195 at bot h concentrations, depressed the contraction amplitude to 80% of the co ntrol value (P < 0.05). In conclusion, Ro 5-4864 had a small but signi ficant depressant effect on the contraction amplitude of human atrial strips. Surprisingly, this effect was not reversed by the peripheral b enzodiazepine receptor antagonist PK 11195.