CARDIORESPIRATORY EFFECTS OF A 5HT(2) ANTAGONIST (R51703) IN AWAKE AND ANESTHETIZED DOGS

To investigate cardiorespiratory effects of an experimental 5-hydroxyt ryptamine receptor antagonist (R51703) with sedative properties, intra muscular doses of the drug were studied in 6 awake dogs of mixed breed , and in 6 anesthetized beagles. Two doses (0.2 and 0.4 mg/kg) of R517 03 and a saline control mere studied in the awake dogs using a randomi zed crossover trial, Subsequently, the higher dose of R51703 was inclu ded as a component of halothane anesthesia to determine whether the ha lothane sparing effect of R51703 produced a beneficial alteration of h emodynamic function. Data were obtained at equipotent halothane/R51703 (H/R) and halothane/saline (H/S) doses equivalent to 1.0, 1.5 and 2.0 MAC, In awake dogs, heart rates tended to be lower in dogs sedated wi th R51703, significantly so at 30 min for both doses, and at 90 and 12 0 min for the 0.2 and 0.4 mg/kg doses, respectively (P < 0.05). The ca rdiac index (CI) was lower at 60 min with both doses compared to the s aline control group. Both doses of R51703 reduced mean blood pressure at 30, 90 and 120 min, and diastolic pressure at 30 and 90 ruin after administration; however, systolic blood pressure (SEP) was not altered . Overall, the cardiovascular alterations were minimal in conscious do gs and there was no evidence of respiratory depression. In the anesthe tized dogs, at equipotent MAC, CI tended to be lower with H/R than wit h H/S, though the difference was not significant. Heart rate and strok e volume index also tended to be lower in the dogs treated with R51703 , while systemic vascular resistance tended to he higher: these change s were not significant, Mean and SBP were higher at each MAC multiple in the H/R group. It was concluded that the halothane sparing effect o f R51703 did not substantially improve hemodynamic function compared t o that use of halothane alone at equipotent doses.