THE EFFECT OF GP683, AN ADENOSINE KINASE INHIBITOR, ON THE DESFLURANEANESTHETIC REQUIREMENT IN DOGS

The availability of an analgesic compound devoid of the side effects a ssociated with the commonly used opioid and nonsteroidal antiinflammat ory drugs would be useful during the perioperative period. Although ad enosine has analgesic and anesthetic-sparing properties, it also produ ces dose-dependent cardiovascular depression. Inhibitors of adenosine kinase may be able to provide analgesia without producing acute cardio vascular or respiratory depression. This preliminary study investigate d the effects of a novel adenosine kinase-inhibiting drug, GP683, on t l-le minimum alveolar anesthetic concentration (MAC) of desflurane in dogs. Seven mongrel dogs were administered one of three different GF68 3 dose regimens (or the solvent) by intravenous infusion on separate o ccasions according to a cross-over study design. After determining the baseline desflurane MAC value, GF683 was infused at 75, 150, or 300 m u g.kg(-1).min(-1) for 5 min as a loading dose, followed by 15, 30, or 60 mu g.kg(-1).min(-1) for an additional 85 min to maintain a stable plasma drug level. The desflurane MAC was redetermined 30-90 min after starting the study drug or vehicle infusion, and 30-90 min and 120-18 0 min after termination of the infusion. Cardiovascular variables and plasma concentrations of GP683 were determined at specific intervals b efore, during, and after the MAC determinations. The three GP683 dose regimens produced 22%, 31%, and 50% decreases in the desflurane MAC, r espectively. In addition, there was good correlation between the decre ase in desflurane MAC and the plasma GP683 concentration (r = -0.78). Although the mean arterial pressure (MAP) was decreased up to 25% by t he highest infusion rate of GP683, adjustments in the desflurane conce ntration to an equi-MAC value resulted in normalization of the MAP val ues. Furthermore, GP683 produced no changes in heart rate. Tn conclusi on, the adenosine kinase-inhibiting drug, GP683, produced dose-depende nt decreases in the desflurane MAC of dogs without producing untoward hemodynamic changes. Implications: An investigational drug (GP683) tha t can increase the levels of an important endogenous substance in the body (adenosine) has been found to decrease the anesthetic requirement in dogs without producing adverse effects on the cardiovascular syste m.