XI. PHARMACOLOGY 467 



hypotensive effect <it' thiamine was markedly (hminislied indicate that the 

 vasodihitation may be of central origin. A moderate decrease in heart rate 

 following the injection of large doses of thiamine may contribute to a minor 

 extent to the fall in blood pressure. 



Thiamine has little, if any, effect on the isolated heart of the frog^' -■ ''■^ 

 or of the turtle.^ Whether the brad.ycardia observed in dogs^' ^' '° is caused 

 In' an action of thiamine on the cardiac vagus or on the medullary centers 

 remains undecided. Studies on the dog heart lung preparation^ have failed 

 to show any change in heart action with concentrations of thiamine far 

 exceeding those which produced hypotension in the intact dog. 



Thiamine is without effect on the isolated intestine of rats, rabbits, and 

 guinea pigs and on the guinea pig uterus.'- ^' " The claim that acetylthi- 

 amine has an acetylcholine-like elTect on the gut'^ has not been confirmed." 

 In large concentrations thiamine inhibits the action of nicotine on the iso- 

 lated intestine of rabbits and guinea pigs without interfering with responses 

 to acetylcholine or epinephrine; the thiazole moiety of the vitamin, 4- 

 methyl-5-hydroxyethylthiazole, has similar effects.'^ Thiamine also pre- 

 \'ents the rise in blood pressure induced by nicotine.'^ It blocks transmission 

 of nerve impulses through the superior cervical ganglion.'^ 



Besides its ganglionic depressant action at large doses, thiamine, in still 

 larger doses, depresses the transmission of impulses to the skeletal muscle 

 at the neuromuscular junction.'^- '^' " In accord with this curare-like action, 

 it has been found to depress the response of the skeletal muscle to acetyl- 

 choline.'^- '' Curarizing elTects could be demonstrated in intact mammals 

 only under artificial respiration following excessive, otherwise lethal doses 

 of thiamine. Curare-like paralysis of the respiratory muscle is not the cause 

 of death by intravenous injection of thiamine, since the diaphragm responds 

 to direct and indirect electrical stimulation at the time respiration has 

 ceased ."* 4-Methyl-5-hydroxyethylthiazole was found to ha\'e curare-like 

 action similar to thiamine.-" 



'P. Kaiser, Pfliiger's Arch, ges Physiol. 242, .504 (1939). 



^ V. Krspamer, Arch, intern, pharmacodiinwuie 63, 261 (1939). 



9 K. M. Boyd and R. W. Dingwall, Quart. J. Pharui. Pharmacol. 14, 209 (1941). 

 loR. Tislowitz and I. Pines, Klin. Wochschr. 16, 923 (1937). 

 " R. Dufait, Arch, intern, pharmacodynamic 66, 274 (1941). 



'■- R. Kuhn, T. Wieland, and H. Huebschmann, Z. physiol. Chcmic 259, 48 (1939). 

 " K. Unna and E. P. Pick, J. Pharmacol. Exptl. Thcrap. 81, 294 (1944). 

 >^ E. P. Pick and K. Unna, J. Pharmacol. Exptl. Thcrap. 87, 138 (1946). 

 '^ H. Mazella and N. Ferrero, Arch, intern, pharmacodynamic 82, 220 (1950). 

 '* V. Demolo, Konyressber. XVI Intern. Physiol. Kongr. II, 19 (1938). 

 " J. \. Smith, P. P. Foa, and H. R. Weinstein, Science 108, 412 (1948). 

 »8 C. Torda and H. G. Wolff, Proc. Soc. Exptl. Biol. Med. 56, S9 (1944). 

 '9D. P. Sadhu, Am. J. Physiol. 147, 2.33 (1946). 

 " J. .\. Smith, P. P. Foa, and H. R. Weinstein, Am. J. Physiol. 155, 469 (1948). 



