Adrenaline Optical isomers

Two synonyms, two definitions, and an expression of admiration. The word norepinephrine is synonymous with noradrenalin, and the word epinephrine is synonymous with adrenalin. The distinctions are that the first in each case is American and the second British. And the term chiral indicates a potential asymmetry in a molecule that would allow eventual separation into two optical isomers. The term racemic refers to a mixture of these two isomers which has not yet been separated into the individual components. A racemic mixture is called a racemate and, from the point of view of the human animal (which is completely asymmetric), must be considered as a mixture of two structurally identical but... 

Epinephrine (adrenaline) was one of the first hormones for which differential effects on blood pressure were reported for the two epimers in the early 20th century [58]. A reassessment of epinephrine activity was made by analyzing the effects of optical isomers of ephedrine and methylephedrine on the spontaneous beating rate of the isolated right atrium of normal and reserpinized rats by investigating direct and indirect actions on al-adrenoceptors. L-ephedrine, and to a lesser extent D-ephedrine, markedly increased the beating rate of rat right atrium [59]. 

The combination of these interactions can generate binding energies in the order of 12-17 kcal M, corresponding to binding constants in the order of 10 to 10 M. The biologically weak optical isomer, S(-l-)-adrenaline, can... 

Murmann, W., Rumore, G. and Gamba, A. (1967) Pharmacological properties of l-(4 -nitrophenyl)-2-isopropylamino-ethanol (INPEA), a new beta-adrenergic receptor antagonist. V. Effects of the optical isomers D(minus) and L(plus) INPEA on heart rate, oxygen consumption and body temperature and on the cardiac and metabolic effects of adrenaline and noradrenaline in urethane-anesthetized rats. Boll. Chim. Farm., 106, 251-268. 

Sympathomimetics are also generally optically active drugs, with only one stereoisomer conferring most of the clinical efficacy of the racemate for instance laevo-noradrenaline is at least 50 times as active as the dextro- form. Noradrenaline, adrenaline and phenylephrine are all used clinically as their laevo-isomers. 

Isomerisation is the process of conversion of a dmg into its optical or geometric isomers. Since the various isomers of a dmg are frequently of different activity, such a conversion may be regarded as a form of degradation, often resulting in a serious loss of therapeutic activity. For example, the appreciable loss of activity of solutions of adrenaline at low pH has been attributed to racemisation - the conversion of the therapeutically active form, in this case the levorotary form, into its less-active isomer. 

Adrenaline is optically active owing to an asymmetric carbon atom in the side-chain. The natural form is the ( + )-isomer, and is much more active than the (— )-isomer. 

Early confirmation of the existence of drug receptors was provided by substances that form pairs of optically-active stereoisomers. Numerous drugs, including morphine, atropine, and adrenaline, can be obtained in two forms, namely as dextro- and laevo-rotatory isomers (see Section 13.1), which differ strikingly in biological potency. Because the two members of such pairs have identical chemical and physical properties, and differ only in that their molecules are built as mirror images of one another, it is evident that the shape of a drug molecule is crucial for its action and that a part of the molecule may have to fit a structure complementary to it (Cushny, 1926). 

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