468 THIAMINE 



Excessive doses of thiamine may produce bronchoconstriction in dogs.-^ 

 Application of a 2 to 10 % solution of thiamine directly to the motor cortex 

 of dogs caused generalized convulsions; this effect was not obtained with 

 either of the two moieties of the thiamine molecule.-^ 



Since thiamine or a thiamine-like substance has been reported to be re- 

 leased together with acetylcholine on electrical stimulation of cholinergic 

 nerves,^^'^* numerous studies have been carried out with the object of 

 studying a possible interdependence of the effects of thiamine and acetjd- 

 choline. Thiamine was found to potentiate the effects of acetylchohne on 

 the leech muscle^^- -^ and on other preparations (for references, see Minz"). 

 The required concentrations of thiamine were large and far beyond those 

 found in normal tissues. Other studies on isolated organs (intestine, uterus, 

 leech muscle, frog heart, frog rectus muscle), however, have failed to dem- 

 onstrate any sensitizing effect of thiamine on the action of acetylcholine; 

 at concentrations of 1 to 10 mg. % in the nutrient solution, thiamine de- 

 pressed the effects of acetylcholine/- *• ^^ Thus, the influence which thi- 

 amine may exert on the reactivity of the tissues to acetylcholine appears 

 not to be sufficiently substantiated to allow general conclusions. Thiamine 

 in large concentrations inhibits cholinesterase.^^' ^' To what extent this 

 action may be involved in some of the pharmacodynamic effects of thi- 

 amine is difficult to assess. Lacking data on the actual acetylcholine levels 

 in the tissues of thiamine-treated animals, there is little reason to compare 

 thiamine to such a potent cholinesterase inhibitor as eserine. Elucidation 

 of the interdependence between acetylcholine and thiamine has already 

 been initiated at the biochemical level; an interdependence with regard to 

 the pharmacological effects of the vitamin has yet to receive unequivocal 

 substantiation. 



The lethal doses of thiamine by various routes of administration have 

 been determined in a number of species.^ On intravenous injection the 

 lethal doses in mice were 125 mg. per kilogram; in rats, 250 mg. per kilo- 

 gram; in rabbits, 300 mg. per kilogram; and in dogs, 350 mg. per kilogram. 

 The ratios of the lethal doses on intravenous injection to those on subcu- 



21 M. Post and J. A. Smith, Am. J. Physiol. 163, 742 (1950). 



22 M. V. Dias, Science 105, 211 (1947). 



23 B. Minz, Compt. rend. soc. biol. 127, 1251 (1938). 

 2< A. von Muralt, Nature 152, 188 (1943). 



26 B. Minz and R. Agid, Compt. rend. 205, 576 (1937). 



26 F. von Bruecke and H. Sarkander, Arch, crptl. Pathol, v. Pharmakol. 195, 

 218 (1940). 



27 B. Minz, La transmission (•liimi(iue de I'inilux nervoux, p. 155. Flammarion, 

 Paris, 1947. 



28 D. Glick and W. Antopol, ./. Pharmacol. Exptl. Thcrap. 65, 389 (1939). 

 23 W. SuUmann and H. Birkhiiuser, Schweiz. med. Wochschr. 69, 648 (1939). 



