TY - JOUR T1 - RELATIONSHIP BETWEEN THE PHARMACOLOGICAL ACTION AND THE CHEMICAL CONSTITUTION AND CONFIGURATION OF THE OPTICAL ISOMERS OF EPHEDRINE AND RELATED COMPOUNDS JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 363 LP - 400 VL - 36 IS - 3 AU - K. K. CHEN AU - CHANG-KENG WU AU - ERLE HENRIKSEN Y1 - 1929/07/01 UR - http://jpet.aspetjournals.org/content/36/3/363.abstract N2 - 1. A series of 24 compounds, 6 of which are optical isomers of ephedrine, have been studied pharmacologically. They are the derivatives of the general formula C6H5·CHH'·CHR·NR'R'' H' = OH or H, and R, R' and R'' = H or alkyl radical respectively. 2. When H' remains OH, R'' remains H, and R or R' becomes methyl or ethyl, the sympathomimetic action is preserved but weakened as compared with β-phenylethylamine, the ethyl being weaker than the methyl derivatives. Those compounds have a mydriatic action. The primary amines are more active than the corresponding methylated secondary or tertiary amines, especially with reference to the pressor action. When R = methyl or ethyl, the compound acquires a prolongation of action and loss of pressor response upon repeated intravenous injections in animals. The methyl members are easily absorbed from the gastrointestinal tract to produce systemic effects in men (ephedrine and nor-d-ψ-ephedrine). 3. The replacement of OH for H' appears to reduce the toxicity and favor the mydriatic action of the compound. 4. With increase in the number of C-atoms in R, R' and R'', the cardiac depressant action increases, the pressor action becomes a depressor action, and the toxicity rises. 5. The majority of the compounds inhibit the isolated rabbit's intestine, stimulate the isolated guinea pig's uterus (virgin), and contract the congested nasal mucous membrane in men. 6. The six optical isomers of ephedrine qualitatively have the same physiological action. The mydriatic action of l-ephedrine and d-pseudoephedrine is greater than that of d-ephedrine and l-pseudoephedrine, respectively. When indirectly compared for pressor action in pithed cats with epinephrine, l-ephedrine is found to be about 3 times as strong as d-ephedrine, and d-pseudoephedrine 7 times as strong as l-pseudoephedrine. l-Ephedrine, the strongest isomer, is 35 times as powerful as l-pseudoephedrine, the weakest isomer of the six. When given by mouth to men in the same quantity, d-ephedrine and l-pseudoephedrine do not raise the systolic blood pressure while the other four isomers do. Of the two sets of isomers d-ephedrine and l-pseudoephedrine have the least toxicity. 7. A discussion of the typical action of ephedrine based on the structure and stereoisomerism has been presented. New compounds have been suggested for study, as they may possess the clinical advantages of both epinephrine and ephedrine. ER -