Is AL-438 likely to have fewer side effects than the glucocorticoids?
The glucocorticoids are effective anti-inflammatory agents but their use may be limited by systemic side effects. AL-438 and prednisolone inhibit binding to glucocorticoid and mineralcorticoid receptors with similar potency. In rat models of acute and chronic inflammation, AL-438 was effective but less potent than prednisolone. In fasted overnight rats, prednisolone was hyperglycaemic but AL-438 was not. Prednisolone also inhibited bone formation in rats, whereas AL-438 did not. The differing profile of AL-438 relative to prednisolone may be due to altered interactions between the receptor and selected co-activators. AL-438 may have lesser side effects than prednisolone.
Doggrell
Sheila
S
School of Biomedical Sciences, University of Queensland, QLD 4072, Australia.
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000009:adverse effects; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000493:pharmacokinetics; D001578:Benzopyrans / Q000009:adverse effects* / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D005786:Gene Expression Regulation / Q000187:drug effects; D005938:Glucocorticoids / Q000009:adverse effects* / Q000493:pharmacokinetics; D007249:Inflammation / Q000235:genetics / Q000473:pathology; D011239:Prednisolone / Q000009:adverse effects; D011804:Quinolines / Q000009:adverse effects* / Q000493:pharmacokinetics; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism
C476829:10-methoxy-5-(2-propenyl)-2,5-dihydro-2,2,4-trimethyl-1H-(1)benzopyrano(3,4-f)quinoline; D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001578:Benzopyrans; D005938:Glucocorticoids; D011804:Quinolines; D011965:Receptors, Glucocorticoid; D011239:Prednisolone