New Indications and New Retinoids

Abstract

In addition to well-accepted indications, etretinate has a beneficial effect in a variety of other dermatoses such as the hyperkeratotic eczema of the palms and soles, prurigo nodularis, and other nonpsoriatic, sterile, pustular eruptions. Due to its influence on dermal inflammatory processes and immunomodulation of the tissue response, etretinate is effective in cutaneous lupus erythematosus, certain bullous disorders like pemphigus herpetiformis, the persistent variant of Grover’s disease, dermatitis herpetiformis, and bullous pemphigoid. Isotretinoin is reported to be effective in cutaneous sarcoidosis, disseminated granuloma annulare, systemic sclerosis and tumors of the cutaneous appendages. New synthetic retinoids have been developed. Etretin, the main metabolite of etretinate, was shown to be effective and to have a short elimination half-life of – 50 h. Arotinoid ethyl ester and arotinoid-free carboxylic acid are effective in minimal doses 500-fold lower than etretinate. Arotinoid ethyl ester was shown not to increase serum lipids. Arotinoid ethyl sulfone is the first retinoid without bone toxicity in animal experiments. Motretinide is the ethylamide of tretinoin and is reported to be effective in the local treatment of acne. Some of the new poly-aromatic retinoids appear to have sebosuppressive, antikeratinizing and/or anti-inflammatory effects via topical application.

IκBβ Interacts with the Retinoid X Receptor and Inhibits Retinoid-dependent Transactivation in Lipopolysaccharide-treated Cells

“…Accordingly, glucocorticoid-mediated inhibition of NFB activity may involve other mechanisms such as the IB␤-RXR interactions described here. The antagonistic interaction is consistent with the fact that LPS is one of the best known pro-inflammatory agents (21), whereas retinoids are anti-inflammatory (22)(23)(24). Thus, exploration of these interactions may lead to new insights into mechanisms of inflammatory signal transduction pathways and possibly the development of new anti-inflammatory agents.…”

Retinoids increase human apo C-III expression at the transcriptional level via the retinoid X receptor. Contribution to the hypertriglyceridemic action of retinoids.

“…Although we cannot exclude that RAR may also contribute to the retinoid-induced hypertriglyceridemia in humans, our results identifying the human apo C-III as a RXR target gene indicate a role for RXR in the retinoid-induced hypertriglyceridemia in humans. Interestingly, the RAR-specific agonist Ro13-6298, the ethylester of TTNPB, does not induce hypertriglyceridemia in humans (60)(61)(62).…”

Retinoid-Induced Hypertriglyceridemia in Rats Is Mediated by Retinoic Acid Receptors

“…arotinoid that can be deesterified to a form, commonly referred to as TTNPB, that transactivates RARs but not RXRs (Loeliger et al, 1980;Gollnink, 1987;Beard et al, 1995). Thus, the hypertriglyceridemic activity of AGN 190121 and Ro 13-6298 cannot be due to RXR agonist activity.…”

“…Interestingly, a potent retinoid whose free acid metabolite binds selectively to RARs, Ro 13-6298, appeared to lack hypertriglyceridemic activity in small-scale clinical trials (Gollnink, 1987;Beard et al, 1995;Merot et al, 1987;Kingston et al, 1983). Vitamin A, ail-trans-RA, and 13-c/i-RA have been shown to induce hypertriglyceridemia when administered orally to rats Erdman, 1979, 1982;Setty and Misra, 1981;Gustafson et al, 1990), suggesting that the rat might be an appropriate animal model in which to study retinoid-induced hypertriglyceridemia.…”