Methylprednisolone potency

The inclusion of an a-methyl group in position 6 of prednisolone will yield 6-a-methylprednisolone, a compound with slightly greater glucocorticoid potency. This small structural modification greatly diminishes the binding of methylprednisolone to transcortin. 

On the hypothesis that the side chain could perhaps be stabilized against such metabolic inactivation by an appropriately placed but otherwise chemically inert substituent, some analogues of cortisone containing a 16a-methyl group were synthesized by Arth et al. [20] in the expectation that the 16a-methyl substituent would enhance potency by protecting the 20-ketone from metabolism. Ultimately, these authors prepared 9-fluoro-16a-methylprednisolone which was the first derivative of fluorocortisol with markedly increased anti-inflammatory activity that was devoid of mineralocorticoid activity. This latter fact supports the concept that it is the presence of 16a-substituents that prevents binding to the mineralocorticoid receptor. Dexamethasone has become Merck s principal marketed anti-inflammatory steroid. 

On a weight-for-weight basis, the antirheumatic potency of triamcinolone is greater than that of prednisolone (-20%) and approximately the same as that of methylprednisolone. Initial improvement following administration of triamcinolone is similar to that noted with other compounds. Reports in the literature, however, indicate that the percentage of patients maintained satisfactorily for long periods has been distinctly smaller than that with prednisolone. 

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