RT Journal Article
SR Electronic
T1 THE RESPIRATORY EFFECTS OF MORPHINE, CODEINE, AND RELATED SUBSTANCES XI. THE INFLUENCE OF THE ACETOXYL GROUP
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 274
OP 288
VO 73
IS 3
A1 MARGARET SUMWALT
A1 HARRY R. OSWALD
A1 HARRY A. LUSK
YR 1941
UL http://jpet.aspetjournals.org/content/73/3/274.abstract
AB How the metabolism, respiratory activity, and heart rate of rabbits are affected by 5 acetylated drugs related to morphine has been studied. 6-Acetyl-α-isomorphine is more depressant than the 4 codeines, acetyl-, acetyldihydro-, acetyliso-, and acetyldihydro-isocodeine. Among the latter, hydrogenation is correlated with the higher ` threshold" doses, and the spatial position of the acetoxyl group designated by "iso-" is correlated with the more rapid decrease of respiratory activity as dosage increases. Among 32 derivatives of morphine and codeine, the influence of the acetoxyl group upon the "threshold" dose for depressing the minute volume of rabbits was compared with that of ethoxyl, methoxyl, hydroxyl, or hydrogen. In 12 out of 14 pairs the acetoxyl compound has proved more strongly depressant than the one containing hydroxyl. Acetoxyl is more potent than methoxyl 6 out of 10 times. It is less potent, however, than ethoxyl or hydrogen in any of the comparable substances available. The hydrogenation of compounds containing acetoxyl, methoxyl, and hydroxyl, tends to obliterate differences in strength among them. Since hydrogenation makes it more difficult to hydrolyze acetoxyl compounds of morphine, we are led to guess that an acetoxyl group attached at carbon-6 exerts its characteristic influence while being detached, rather than as a part of the molecule.