Inactivity of Coramine (Nikethamide) for L. arabinosus and its Conversion to an Active Substance.

Abstract

The question of relative activities of various derivatives of nicotinic acid for L. arabinosus and for animals has been brought to the front by the discovery of a substance in wheat bran and in certain other materials which is inactive for L. arabinosus but is made active by very mild alkali treatment or moderately strong treatment with acid. 1 , 2 This situation has led to some feeling of unrest in regard to the validity of assay results obtained with L. arabinosus using alkali or acid treatment of the samples. Studies to date 3 , 4 indicate that the animal can utilize derivatives of nicotinic acid more readily than can L. arabinosus. The results of the present study support this finding.

Since nikethamide (pyridine β-carboxylic acid diethyl amide) has been found to be quite active for dogs and humans, 5 , 6 , 7 we tested it on L. arabinosus 0.03% of the activity of an equimolar amount of nicotinic acid. This activity may be due to impurities or slight conversion during sterilization. Glenn et al. 4 have reported nikethamide to be inactive for this organism. Dorfman et al. ⁸ have found it to be slightly active for dysentery bacilli, while Knight⁹ and Landy¹⁰ have found it inactive for Staph, aureus.

The compound was autoclaved for one hour with various concentrations of NaOH, HCl, and H₂SO₄ at 15 pounds and the resulting mixtures were assayed with L. arabinosus. The results summarized in Fig. 1 show that NaOH is most effective, while HCl is somewhat more potent than H₂S0₄ in converting nikethamide to an active compound. Nikethamide is less easily converted to active material than is the “precursor” found in wheat bran, since autoclaving with 0.1 N NaOH, 1 N HCl, or 1 N H₂S0₄ seems to bring about 100% conversion of the latter substance.