Statistics Notes: The use of transformation when comparing two means

(1) Twenty-one synthetic compounds, all of them benzilic esters of alkamines, have been tested for mydriatic activity in the mouse; seven of them proved to be powerful mydriatics, comparable in intensity of action with atropine but shorter in duration. (2) Fifteen of them were tested in the cat for atropine-like action in the salivary gland and on the blood pressure. The powerful mydriatics were all more active than atropine in both respects, and several compounds weaker than atropine in mydriatic activity were more active than atropine in the salivary gland. (3) Several of the compounds were found to be atropine-like in smooth muscle and in the isolated cat9s heart. (4) Eight of the more active mydriatics were tested for toxicity; in mice all of them were more toxic than atropine on intraperitoneal or subcutaneous injection but two of the most promising compounds (E3 and P10) were less toxic than atropine on oral administration; the same two compounds produced much less severe symptoms on subcutaneous injection into cats than atropine did in equal doses. (5) Benzilic esters of quaternary alkamines were in general more active in all the tests used than those of corresponding tertiary alkamines. (6) The mydriatic activity of the quaternary metho-salts of atropine, l-hyoscyamine, l-hyoscine and eucatropine has been compared with that of their parent bases in the mouse pupil and after local application to the eye of the cat. In the mouse the metho-salts, except l-hyoscine methiodide, are more active than the tertiary bases; in the cat the tertiary bases are the more active mydriatics. (7) The relations between chemical structure and atropine-like action among the synthetic compounds and the belladonna alkaloids are discussed. (8) Among the synthetic benzilic esters benzilyloxyethyl dimethylethyl ammonium chloride (E3) appears to be the most promising substitute for atropine in ophthalmic practice; its action equals that of atropine in intensity but is shorter in duration and its toxicity compares favorably with that of atropine.