Cardiac action of thiamine derivatives in guinea pig atria.
Pharmacological studies were performed on allithiamine (TAD), thiamine propyl disulfide (TPD), and thiamine tetrahydrofurfuryl disulfide (TTFD) to investigate positive inotropic and negative chronotropic effects seen when they are applied to spontaneous beats in isolated guinea pig atria at concentrations higher than 10-5 g/ml. 1. The effects of thiamine 8-(methyl-6-acetyldihydrothioacetate) disulfide (TATD) and thiamine hydroxyethyl disulfide (TOED) at 5 x 10-4 were slight, and those of dibenzoyl thiamine (DBT) and thiamine were limited at any concentration. 2. Dimethyl propyl disulfide (DMPD) which has anti-thiamine activity, showed these effects at concentrations higher than 10-5. 3. The negative chronotropic effect of TAD, TPD, and TTFD was not influenced by the prior application of atropine, and the positive inotropic effect was not influenced by propranolol. 4. The effects of TTFD on the electrically driven left atrial muscle were remarkable when the muscle was driven at low frequency, while they were less remarkable at high frequency. 5. The decrease in tension of the electrically driven left atria induced by mersalyl at 5 x 10-4 g/ml was recovered by the subsequent addition of TTFD or TPD at 5 x 10-4 as well as dimercaprol at 5 x 10-5. From the results, it was assumed that (a) the effects of TAD, TPD and TTFD might relate to their common chemical structure of the disulfide, especially to the alkyldisulfide chain, (b) the effects are irrevelant to their common activity as an vitamin B1 and to either cholinergic or adrenergic effect, and (c) a mutual dependence is seen between the positive inotropic effect and the negative chronotropic effect.
D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D016275:Atrial Function; D001285:Atropine / Q000494:pharmacology; D004112:Dimercaprol / Q000494:pharmacology; D004220:Disulfides / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005260:Female; D005666:Fursultiamin / Q000494:pharmacology; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects; D008297:Male; D008634:Mersalyl / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects; D013329:Structure-Activity Relationship; D013831:Thiamine / Q000031:analogs & derivatives* / Q000494:pharmacology
D000963:Antimetabolites; D004220:Disulfides; D005666:Fursultiamin; D004112:Dimercaprol; D008634:Mersalyl; D001285:Atropine; D013831:Thiamine