Action of Synthetic Vitamin B. 1

Abstract

The antineuritic vitamin, B₁, has been crystallized by different groups of investigators,^1-6 but it remained for Williams and his associates7 to arrive at a correct structural formula, confirmed by successful synthesis. 8

For some time, the crystalline vitamin B₁, both the natural and the synthetic, has been available in the form of the hydrochloride in our laboratory for pharmacological studies. Our results appear so uniform that they can probably serve as an additional proof to that established by chemical means, concerning- the identity of the two products.

To determine the potency of the synthetic vitamin B₁, rats were made definitely polyneuritic and treated with various doses according to the technique of Smith, 9 except that a small amount (0.4%) of Brewers'yeast was added to the diet, as suggested by Dann, 10 in order to reduce the incidence of deaths. Tests were also carried out in pigeons rendered polyneuritic by the diet proposed by Cowgill 11 for confirmative purposes.

As shown in Table I, doses of 0.004 to 0.006 mg. of synthetic vitamin given by mouth were sufficient to cure 77 to 85% of the rats. An amount of 0.003 mg. was effective in one case but failed in the other 2, so that the minimal curative dose of the vitamin by mouth in rats was 0.004 mg. in the present series of experiments. In 9 pigeons, a dose of 0.005 mg. injected intravenously abolished the symptoms of polyneuritis in 4 animals for 2 to 3 days, and in 5 for 4 days or more. The figures in this investigation with both rats and pigeons correspond closely to those reported by other workers for the natural crystalline vitamin, 6 , 12 ,¹⁴ and fully confirm those claimed by Williams and Cline 8 for their synthetic product.

Other pharmacological effects are also similar when the natural and the synthetic compounds are compared side by side. In an etherized cat weighing 2.63 kg., doses of 5, 20, and 50 mg. of the synthetic product, injected intravenously, caused a slight decrease in respiratory volume, but no changes in respiratory rate, blood pressure, or heart rate. Similar effects were observed with the same doses of the natural vitamin. Neither substance produced congestion or necrosis in the rabbit's ear by subcutaneous injection in the dosage of 1 mg. dissolved in 0.1 cc. of saline. The minimal lethal dose (M.L.D.) in guinea pigs is the same with both the natural and the synthetic products, by intravenous injection, as shown in Table II. The vitamin solution employed for the toxicological study was 2% in each case, and the weight of the animals varied from 210 to 265 gm. Clonic convulsions occurred after doses of 150 mg. per kg., or more, had been administered. Those animals which survived the sublethal doses recovered completely within 1½ and 5 minutes, apparently without any after effects.