EFFECTS OF THIAMINE DERIVATIVES ON THE ATRIAL TRANSMEMBRANE POTENTIALS AND SPONTANEOUS CONTRACTION IN THE RABBIT

Abstract

Since the role of thiamine pyrophosphate in the metabolism of α-keto acids has been biochemically established, many investigations have been devoted to understand its biological activity on the enzymatic mechanism. Recently, various derivatives of thiamine have been synthesized and found to be active in several enzyme systems in the brain, peripheral nerve, heart and liver (1-3).
On the other hand, it has been reported that thiamine in higher concentration produces a negative inotropic effect in the isolated heart of the turtle and the heartlung preparation of the dog as well as in the isolated atrium of the cat (4, 5). The synthesis of alkyldisulfide and carboethoxy derivatives of thiamine and their wide clinical uses in comparatively large doses prompted the re-examination of the pharmacological contribution of thiamine for the clinical indications. More recently, it has been demonstrated that these derivatives in higher concentration produce a positive inotropic effect on the isolated atrium of the guinea pig (6, 7) and restore the cardiac depression caused by a variety of carbohydrate metabolic inhibitors (8, 9), and that thiamine and its derivatives prolong the repolarization time of the atrial action potential in the guinea pig (7).
It has been speculated that the cardiac cholinergic nerve liberates thiamine when it is activated, and thiamine plays an essential role in the maintenance of the physiological function of the peripheral nervous system (1), and that thiamine may be an inhibitor of cholinesterase activity (10). Moreover, it has been reported that thiamine derivatives produce blocking effects on the sympathetic ganglion (11) and the neuro-muscular junction (12).
In the present paper, the effects of thiamine hydrochloride and its derivatives on the spontaneous contraction and the transmembrane potentials of the isolated atria of the rabbit were investigated in an attempt to know the relationship between their pharmacodynamic effects and biochemical ones.