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Pharmacologic interventions after an LD50 cocaine insult in a chronically instrumented rat model: are beta-blockers
M Smith1, D Garner, J T Niemann
1UCLA School of Medicine, Department of Emergency Medicine, Torrance 90509.
Study Purpose:
To evaluate drug management of acute cocaine toxicity in a new animal model. The study null hypothesis was that no drug would affect outcome compared with a placebo control.
Model:
Chronically instrumented, conscious, unrestrained rats subjected to an LD50 dose (1.4 mg/100 g body wt) of IV cocaine.
Methods:
Rapid injection of IV cocaine by IV vascular access port followed by injection of therapeutic study drugs. Outcome (survival vs death) with drug treatment was compared with a placebo group. PHARMACOLOGIC INTERVENTIONS: Normal saline placebo (0.2 mL/100 g), diazepam (0.5 mg/100 g), chlorpromazine (0.2 mg/100 g), propranolol (1.0 mg/100 g), labetalol (3.0 mg/100 g), or verapamil (0.1 mg/100 g) was given. There were ten rats in each treatment group. Allocation to treatment groups was nonrandomized.
Statistical Methods:
Fisher's exact test.
Results:
IV injection of cocaine was followed by tonic-clonic seizure activity in all treatment groups. No study drug significantly improved survival compared with the placebo group. However, no animal treated with propranolol survived (P less than .05 vs saline control), and only one of ten animals treated with labetalol survived (P = .14 vs placebo group).
Conclusion:
In this conscious animal model subjected to an LD50 IV cocaine insult, chlorpromazine and diazepam, previously shown to be of value in other animal models, had no effect on survival. Verapamil also did not affect outcome. Outcome was adversely affected by treatment with beta-blocking agents.