The action of optical isomers

Abstract

IN a former paper' it was shown that the two hyoseyamines differ to a marked extent in their pharmacological action, the laevorotary natural base possessing a very powerful action on the terminations of the nerves in the salivary glands, heart, and iris, while the dextrorotary artificial base is almost devoid of effect on these organs, but exercises a stronger stimulating action on the central nervous system of the frog. The action of atropine (racemic hyoscyatmiine) is the resultant of the action of its two components, lavo-and dextro-hyoseyamine, and it thus affects the nerve terminations about half as strongly as levo-hyoscyamine, while possessing a more distinct stimulant action on the central nervous system. The difference in the effect of-lhevo-hyoscyamine and the dextrorotary alkaloid was first inferred from a comparison of the actioif of atropine and hyoseyamine, and was then confirmed by the study of dextro-hyoscyamine.A review of the literature concerning the action of optical isomers on vertebrates was given in that paper but two further examples of differentiation between the isomers have since been added. Mayor2 states that levo-nicotine, the natural alkaloid, is twice as toxic to guineapigs as the artificial dextro-nicotine. The lavorotary base irnduces pain when injected hypodermically, while the dextrorotary has nio such effect, and there appears to be some difference in the nature of the convulsions, those following dextro-nicotine having a prevailing tremulous character, while those induced by levo-nicotine are more violent and set in more abruptly. Neuberg and Mayer3 found that d-mannose' undergoes more rapid oxidation in the tissues of the rabbit than 1-mannose, and that the injection of inactive mannose is followed by the appearance of 1-and inactive mannose in the urine. Glycogen is formled from inactive

Functional Selectivity of GPCR Ligand Stereoisomers: New Pharmacological Opportunities

“…It has been known for a century that the naturally occurring (Ϫ)-stereoisomer of epinephrine constricts blood vessels more potently than (ϩ)-epinephrine (Cushny, 1908). Since then, a large number of studies has elaborated the concept that (Ϫ)-stereoisomers of catecholamines bind to adrenergic receptors with higher affinity and activate the receptors with higher potency than the corresponding (ϩ)-stereoisomers.…”

Robust estimation of the Birnbaum-Saunders distribution

“…influence function of T a t the mode1 Fe, definecl in (27) function defineci in (19) fisher information matrix of the vector 8 harmonic mean function defined in (14) load in the ith time step [a load step] least median of squares lest squaxes number of groups used for jackknife estimator defined in (18) 2 x 2 matrix defined in (29) cumulative distribution iunction of C defined in (4) probability density function optimal B-robust estimator(s) a probability between zero and one defined in (21) mots of (12) of Theorem 2 2 x 2 matnx defined in (42) harmonic mean defined in (13)…”

“…Birnbaum-Saunders distnbuted random variable dehed in (21) estimator of 0 pt h quant ile of the Birnbaum-Saunders distribution, defined in (23) confidence interval for t,, defined in ( optimal B-robust estimate of a location and scale parameter of the Bimbaum-Saunden distribution mean mean estimate of p defined in (17) jackknife estimator of fl defined in (18) mean mean estimator excluding the ith group maximum likelihood estirnate of fl [ …”

“…To m y dear father Raymond G. Mills List of Symbols and Abbreviations 2 x 1 vector defined implicitly thsough (32) least squares estirnate of the slope of the line y = a + bx 2 x 2 matrix defined implicitly through ( Birnbaum-Saunders farnily of distributions size of groups used for jackknife estimator defined in (18) function defined in (15) …”

Using R for Data Analysis: A Best Practice for Research

“…We will demonstrate a paired-samples t test using the data from Cushny and Peebles (1905), which was used by Gosset ("Student") to demonstrate the theoretical developments of the t distribution (Student, 1908). The data are the average number of hours of sleep gained by 10 patients on two different drugs, Dextro-hyoscyamine hydrobromide and Laevo-hyoscyamine hydrobromide.…”