The comparative hemodynamic effects of intravenous IQB-9302 and bupivacaine in anesthetized rats

Background: The new local anesthetic IQB-9302 is an amide derivative bearing a cyclopropyl group, with remarkable long duration of action and relative low toxicity. In trying to characterize further its safety profile, the current study compared the hemodynamic effects of different concentrations of bupivacaine and IQB-9302 with saline. Methods: Two groups of eight anesthetized Sprague–Dawley rats were given 0.1, 0.3, 1, 3, and 10 mg/kg of intravenous (i.v.) IQB-9302 or bupivacaine at 20-min intervals; control animals received saline only. Arterial blood pressure and heart rate were monitored during the following 20 min. Results: Both bupivacaine and IQB-9302 reduced heart rate: for bupivacaine, −73.8 beats per min (bpm) (SD: 103.8) and −132.5 bpm (SD: 140.7) at 1 and 3 mg/kg, respectively; for IQB-9302, the reduction amounted to −40.8 bpm (SD: 14.2) and −113.5 bpm (SD: 94.2) at 1 and 3 mg/kg, respectively (baseline range, 318.7–438.2 bpm). The two drugs also produced a comparable increase in the mean arterial blood pressure; bupivacaine increased it by 8.7 mmHg (SD: 6.6) and 12.6 mmHg (SD: 15.4) at 1 and 3 mg/kg, respectively, and IQB-9302, 18.7 mmHg (SD: 21.1) and 20.7 mmHg (SD: 20.5) at 1 and 3 mg/kg, respectively (baseline range, 47.4–134.1 mmHg). All rats treated with 10 mg/kg of either drug died after a drop in heart rate and mean arterial blood pressure. Conclusion: IQB-9302 had hemodynamic effects similar to those of bupivacaine in anesthetized rats. The clinical relevance of these effects warrants further investigation.