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Terazosin: intravenous safety evaluation in rats
Drug and Chemical Toxicology
|January 1, 1984
Summary
Terazosin, an alpha-adrenergic antagonist, showed an LD50 of 277 mg/kg in male rats and 293 mg/kg in females. The no-toxic-effect level was 40 mg/kg/day, with higher doses causing hypothermia, cardiorespiratory failure, and death.
Area of Science:
- Pharmacology
- Toxicology
- Cardiovascular Research
Background:
- Terazosin is an alpha-adrenergic antagonist.
- Understanding its toxicological profile is crucial for safe clinical use.
Purpose of the Study:
- To determine the lethal dose 50 (LD50) of terazosin in rats.
- To establish the no-toxic-effect dosage (NTED) and characterize toxicity following subchronic administration.
Main Methods:
- Intravenous administration of terazosin to male and female rats.
- Daily oral administration for 1 month at various dosages (0, 10, 40, 150 mg/kg/day).
- Monitoring for mortality, clinical signs of toxicity, and performing necropsies.
Main Results:
- The LD50 was determined to be 277 mg/kg for males and 293 mg/kg for females.
- The no-toxic-effect dosage was established at 40 mg/kg/day.
- Toxicity at 150 mg/kg/day included hypothermia, hypoactivity, blepharoptosis, ptyalism, splenic congestion, and death due to cardiorespiratory failure.
Conclusions:
- Terazosin exhibits dose-dependent toxicity in rats, with acute toxicity leading to cardiorespiratory failure.
- The established no-toxic-effect dosage provides a reference for safe dosing levels in preclinical studies.