Peraclopone

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Peraclopone is a hypolidemic drug. It is an inhibitor of 7-Dehydrocholesterol reductase. Peraclopone potently inhibits the final step in cholesterol biosynthesis. Feeding this agent to rats leads to a rapid replacement of membrane cholesterol with its immediate precursor 7-dehydrocholesterol, and a dramatic reduction in plasma sterol concentration. Peraclopone caused a dose-dependent decrease in cholesterol and a concomitant accumulation of provitamin D3 (7-dehydrocholesterol) in the skin, which is accompanied by an increase in the plasma level of 25-hydroxyvitamin D3. Treatment with peraclopone dramatically alters membrane sterol content in many membranes including the microvillus membrane of both the jejunum and ileum. In the jejunal microvillus membrane a major change in chemical composition occurred, presumably in response to the alteration in membrane sterol. The net result was a significant decline in both the static and dynamic component of membrane fluidity.