Isomerism (Alkaloids)

1.5 Isomerism

Generally, isomerization is the process of involving the change of one structure into another having the same emperical formula but with different properties in one or more respects.
A plethora of alkaloids contain one or more asymmetric carbon atoms in the molecule, and hence exhibit optical activity. It has been observed that in the majority of instances only the (–)- isomer (i.e., the levorotatory component) has appreciable and distinct pharmacological activity than the corresponding (+)-isomer (i.e., the dextrorotatory, component) of the same alkaloidal species.
At this juncture, one needs to understand clearly the traditional designations l- and d- for the levo- and dextro- rotatory isomers respectively; and these are to distinguished from the designations L- and D- which refer not to the optical activity, but to the steric configuration with regard to a conventionally accepted reference compound.
In fact, the optical activity is invariably associated with the alkaloids and their respective salts. However, the optical activity and the specific rotation usually varies with the solvent used, the temperature, the wave length of light and other minor factors.
There are quite a few typical and glaring examples that may serve to illustrate the considerable difference in the pharmacological activity observed amongst the different isomers of an alkaloid.
Examples
(a) Showing d- and l-isomers with distinct pharmacological activities, such as:
(i) Relative pressor activities* of D(–)-ephedrine and D(+) ephedrine: The relative pressor activities of D(–)-ephedrine is found to be 36 with regard to its D(+)-ephedrine isomer at ll i.e., the former is almost 3½ times more active than the latter as shown below:

D(–)-ephedrine and D(+) ephedrine
(ii) Antimigraine activity of (–)-ergotamine and (+)-ergotamine: It has been observed that the antimigraine activity of (–)-ergotamine possesses 3-4 times more activity than its corresponding (+)-ergotamine isomer:

(–)-ergotamine and (+)-ergotamine
(b) Showing both (–)-and (+)-forms active pharmacologically: In certain alkaloids, the (–) form as well as the (+) form are medicinally useful. Examples: The (–)-Quinine is primarily employed as a potent antimalarial agent; whereas the (+)-Quinine, also known as quinidine, is solely used in restoring cardiac arrythmia to normal rythm, as given below:

quinidine
(c) Exception: The (+) (+)–d-tubocurarine of d-tubocurarine is the only isomer that exhibits muscle relaxant properties, as shown below:
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* Increase of arterial blood-pressure.

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