Lastly, simultaneous substitution of the H of the HO group by ethyl and the substitution of an alkyl for the H in the NH group gave the following results:-- =Methyl.=--In dogs the narcotic action was strengthened, the methæmoglobin in the blood diminished. In men the narcotic action was also more marked as well as the anti-neural action. The stomach and kidneys were also stimulated. =Ethyl.=--In dogs the narcotic action was much strengthened, while the methæmoglobin was diminished. In men the antipyretic and anti-neural actions were unaffected. =Propyl.=--In dogs the narcotic action was feebler than with methyl or ethyl, and in men there was diminished antipyretic action. =Amyl.=--In dogs the narcotic action was much smaller. From this latter series the conclusion is drawn that the maximum of narcotic action is obtained by the introduction of methyl and the maximum antipyretic action by the introduction of methyl or ethyl. The ethyl substitution is, as before, the less toxic.[36] [36] _Ueber die physiologische Wirkung des p-amido-phenol u. einiger Derivate desselben._ O. Hinsberg u. G. Treupel, _Archiv f. Exp. Pathol. u. Pharm._, B. 33, S. 216. The effect of the entrance of an alkyl into the molecule of a substance is not constant; sometimes the action of the poison is weakened, sometimes strengthened. Thus, according to Stolnikow, dimethyl resorcin, C₆H₄(OCH₃)₂, is more poisonous than resorcin C₆H₄(OH)₂. Anisol C₆H₅OCH₃, according to Loew, is more poisonous to algæ, bacteria, and infusoria than phenol C₆H₅OH. On the other hand, the replacement by methyl of an atom of hydrogen in the aromatic oxyacids weakens their action; methyl salicylic acid O.CH₃ / C₆H₄ \ COOH is weaker than salicylic acid OH / C₆H₄ . \ COOH Arsen-methyl chloride, As(CH₃)Cl₂, is strongly poisonous, but the introduction of a second methyl As(CH₃)₂Cl makes a comparatively weak poison. § 25. In some cases the increase of CO groups weakens the action of a poison; thus, in allantoin there are three carbonyl (CO) groups; this substance does not produce excitation of the spinal cord, but it heightens muscular irritability and causes, like xanthin, muscular rigidity; alloxantin, with a similar structure but containing six carbonyl groups, does not possess this action. NH--CH--NH | | | CO | CO | | | NH--CO NH₂ Allantoin. NH--CO CO--HN | | | | | | O | | | |/ \| | CO--C---C CO | | | | NH--CO CO--HN Alloxantin.