Pharmacologic interventions after an LD50 cocaine insult in a chronically instrumented rat model: Are beta-blockers contraindicated?
✍ Scribed by Marc Smith; Daniel Garner; James T Niemann
- Book ID
- 104310848
- Publisher
- Elsevier Science
- Year
- 1991
- Tongue
- English
- Weight
- 480 KB
- Volume
- 20
- Category
- Article
- ISSN
- 1097-6760
No coin nor oath required. For personal study only.
✦ Synopsis
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 w~th a placebo control.
Model: Chronically instrumented, conscious, unrestrained rats subjected to an LDso dose (1.4 mg/lO0 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 w~th a placebo group.
Pharmacologic interventions: Normal saline placebo (0.2 mL/lO0 g), diazepam (0.5 mg/lO0 g), chlorpromazine (0.2 mg/lO0 g), propranolol (1.0 mg/lO0 g), labetalo] (3.0 mg/lO0 g), or verapamil (0.1 mg/lO0 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 < .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 LDso 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 p-blocking agents.