Calcium channel blockade: possible explanation for thioridazine's peripheral side effects.
The authors show that thioridazine possesses calcium antagonist activity which may relate to its cardiac and sexual side effects. Binding sites associated with voltage-operated calcium channels were labeled by 3H-nitrendipine. Thioridazine influenced this binding of 3H-nitrendipine in a fashion similar to known calcium antagonists such as verapamil. Thioridazine also antagonized potassium-induced, calcium-dependent contractions of rat vas deferens, with similar potency. Thioridazine concentrations that exert calcium channel antagonist effects correspond to blood levels at therapeutic doses.
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced*; D002121:Calcium Channel Blockers / Q000378:metabolism; D004542:Ejaculation / Q000187:drug effects*; D005260:Female; D007473:Ion Channels / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009543:Nifedipine / Q000031:analogs & derivatives / Q000378:metabolism; D009568:Nitrendipine; D011437:Propylamines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012735:Sexual Dysfunction, Physiological / Q000139:chemically induced; D013881:Thioridazine / Q000009:adverse effects* / Q000097:blood / Q000494:pharmacology; D013976:Tiapamil Hydrochloride; D014649:Vas Deferens / Q000187:drug effects; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D007473:Ion Channels; D011437:Propylamines; D009568:Nitrendipine; D014700:Verapamil; D009543:Nifedipine; D013881:Thioridazine; D013976:Tiapamil Hydrochloride