Background: We hypothesized that the alkaloid compounds that are the majority components of fire ant (Solenopsis invicta) venom are capable of producing cardiovascular and central nervous system toxic effects in mammals.
Objective: To evaluate toxic effects of synthetic S. invicta alkaloids in rodent models.
Methods: Cardiovascular effects of intravenous injection of the racemic (+/-)-cis- and trans-isomers of 2-methyl-6-nundecylpiperidine (isosolenopsin A and solenopsin A, respectively) were evaluated in anesthetized, gallamine-paralyzed rats who had received artificial ventilation and in isolated, perfused rat hearts.
Results: (+/-)-Solenopsin A dose dependently (3-30 mg/kg [10 to 104 micromol/kg]) depressed cardiovascular function. Maximal percent changes following injection of 30 mg/kg were -42.96% +/- 5.8% for blood pressure, -29.13% +/- 3.6% for heart rate, and -43.5% +/- 9.2% for left ventricular contractility (dP/dt). (+/-)-Isosolenopsin A (3-15 mg/kg [10 to 52 micromol/kg]) produced responses similar to those seen with the corresponding doses of solenopsin A. In conscious, spontaneously breathing rats, solenopsin A (30 mg/kg intravenously) caused seizures, respiratory arrest, and death. Infusion of working, isolated, perfused hearts with solenopsin A reduced contractile function (dP/dt) at 10 microM and caused cardiac arrest at 100 microM.
Conclusions: Two alkaloid components of imported fire ant venom possess robust cardiorespiratory depressant activity and elicit seizures in the rat. Such effects identify these alkaloids as toxic compounds in biological systems and may explain the cardiorespiratory failure noted in some individuals who experience massive fire ant stings.