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 benzodiazepine 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 both concentrations, depressed the contraction amplitude to 80% of the control value (P < 0.05). In conclusion, Ro 5-4864 had a small but significant depressant effect on the contraction amplitude of human atrial strips. Surprisingly, this effect was not reversed by the peripheral benzodiazepine receptor antagonist PK 11195.
Shany
E
E
Pediatric Division, Soroka Medical Center, Beersheba, Israel.
Hochhauser
E
E
Halpern
P
P
Vidne
B
B
Gavish
M
M
Geller
E
E
Hasharoni
A
A
Barak
Y
Y
Yakirevich
V
V
D000328:Adult; D000368:Aged; D001570:Benzodiazepinones / Q000494:pharmacology*; D003864:Depression, Chemical; D004594:Electrophysiology; D005260:Female; D058787:GABA-A Receptor Antagonists; D006801:Humans; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects*
D001570:Benzodiazepinones; D058787:GABA-A Receptor Antagonists; D007546:Isoquinolines; C028513:4'-chlorodiazepam; C037850:PK 11195