Phα1β cardiovascular safety pharmacology using the telemetry system in rats

Phα1β, a peptide toxin purified from Phoneutria nigriventer spider venom, has a dual antinociceptive effect, inhibiting high-voltage-activated calcium channels and antagonising the TRPA1 receptor that differentiates it from other traditional analgesics. Safety pharmacology studies conducted during the nonclinical development of new drug candidates include the potential effects of the drug, on cardiovascular parameters. The present study, cardiovascular assessments of Phα1β performed in conscious male Sprague-Dawley rats, previously implanted with the DSI™ PhysioTel telemetry system in the abdominal aorta. Animals received either Vehicle (PBS, 1 mL/kg) or the test compound ST-164 (Phα1β) at doses of 0.2, 0.8 or 2 mg/kg, administered intravenously. Cardiovascular parameters systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), heart rate (HR), body temperature, and electrocardiographic (ECG) readings were evaluated at baseline and at multiple time points post-dosing (0.5, 1, 1.5, 2, 3, 4, 5, and 24 h) post administration of ST- 164 (0.2, 0.8 and 2 mg/kg) resulted in minor, transient, and dose-independent changes in SBP, DBP, MAP, and HR compared to baseline values, with no statistically differences to the vehicle group. A slight, transient, and non-physiologically change in body temperature was observed only at the highest dose (2 mg/kg). Electrocardiographic analysis revealed no alterations in QRS, QT, QTc, or PR intervals at any time point with ST-164 compared to Vehicle. All values were consistent with cardiovascular parameters in Sprague-Dawley rats. The telemetry assay validation with atenolol shows that atenolol reduced systolic blood pressure and mean arterial blood pressure validating the test.