466 THIAMINE 



thought to be an indication of the state of thiamine nutrition before any 

 chnical signs of thiamine deficiency occurred. 



Mouriquand and Coisnard'^^ observed that pigeons on a thiamine-poor 

 diet demonstrated a fall in the chronaxy of the nerves and that this fall 

 begins before the clinical signs appear. 



XI. Pharmacology 



KLAUS R. UNNA 



Thiamine has been shown to produce a variety of pharmacologic effects. 

 It should be borne in mind that these effects have been obtained in experi- 

 mental animals maintained on adequate diets only on parenteral adminis- 

 tration of thiamine in doses several thousand times larger than those 

 required for optimum nutrition. These pharmacologic effects in animals 

 have no counterpart in the therapeutic use of the vitamin in man. 



Death after intravenous injection of thiamine in animals is due to de- 

 pression of the respiratory center.^"* The heart is still beating at the time 

 of cessation of the respiration. Artificial respiration enables the animals to 

 survive otherwise lethal doses ;^ doses of thiamine resulting in concentra- 

 tions of 7 to 10 mg. % in the blood were fatal to dogs (under ether anes- 

 thesia), whereas blood levels of 36 mg. % were tolerated when artificial 

 respiration was provided. 



Rapid intravenous injections of 5 to 50 mg. per kilogram cause a transient 

 fall in blood pressure in cats and dogs which increases with increasing 

 dosage of thiamine. The fall in blood pressure is not influenced by atropine 

 or antihistamines; it may be accentuated after adrenergic blockade with 

 dibenamine.^' ^ There is evidence that the fall in blood pressure is due to 

 thiamine acting at several sites: on the vascular smooth muscle itself, on 

 the vasomotor center, and on the heart. Perfusion experiments on the 

 rabbit's ear and on various arterial areas in dogs have shown that part of 

 the vasodilator effect obtained was due to the acidity of the highly con- 

 centrated thiamine solution. Experiments on decapitated cats in which the 



2^ G. Mouriquand and J. Coisnard, Presse med. 1944, 277. 



1 H. Molitor and W. L. Sampson, E. Merck's Jahresber. 51, 3 (1936). 



2 G. Hecht and H. Weese, Klin. Wochschr. 16, 414 (1937). 



3 J. A. Smith, P. P. Foa, H. R. Weinstein, A. S. Ludwig, and J. M. Wertheim, J. 

 Pharmacol. Exptl. Therap. 93, 294 (1948). 



"T. J. Haley, Proc. Soc. Exptl. Biol. Med. 68, 153 (1948). 



^ H. Mazella, Arch, intern, pharmacodynamie 86, 434 (1951). 



6 S. II. Jaros, A. L. Wnuck, and E. J. de Beer, Ann. Allergii 10, 291 (1952). 



