Toxicity studies with pure trans-capsaicin delivered to dogs via intravenous administration.
Previous toxicology and pharmacology studies have reported variable acute cardiac effects of capsaicin, primarily involving hypotension and bradycardia. However, these studies have suffered from two important limitations. First, the capsaicin tested has been derived from pepper plant extracts, which is likely to display varying degrees of purity and possibly diverse impurity profiles. Second, post-dosing follow-up was generally limited to three or fewer days. Therefore, the objective of the studies reported here was to test the cardiac and other target organ toxicity potential of pure, synthetic trans-capsaicin (the only naturally occurring stereoisomer of capsaicin) when delivered via intravenous administration to dogs either acutely or for 14 days. Taken together, results from these two studies indicate that pure trans--capsaicin--even when delivered directly into the systemic circulation at high dose levels--is rapidly eliminated, induces transient tachycardia and hypertension, does not alter the duration of cardiac action potentials, and causes only very minimal organ toxicities. The different toxicity profiles of pure trans-capsaicin reported here and chili pepper extracts previously reported suggest that the purity and source of capsaicin should be an important consideration for toxicological evaluations.
Chanda
Sanjay
S
NeurogesX, Inc., 981F Industrial Road, San Carlos, CA 94070, USA. schanda@neurogesx.com
Mould
Andrew
A
Esmail
Ashiq
A
Bley
Keith
K
D000818:Animals; D001772:Blood Cell Count; D002211:Capsaicin / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D002319:Cardiovascular System / Q000187:drug effects*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004798:Enzymes / Q000097:blood; D005260:Female; D006973:Hypertension / Q000139:chemically induced; D007275:Injections, Intravenous; D008297:Male; D012137:Respiratory System / Q000187:drug effects*; D012737:Sex Factors; D013237:Stereoisomerism; D013610:Tachycardia / Q000139:chemically induced; D013997:Time Factors
D004798:Enzymes; D002211:Capsaicin