Discovery and development of statins as they directly compete with the endogenous substrate for the active site cavity of HMGR. Statins are also noncompetitive with the cosubstrate NADPH (nicotinamide adenine dinucleotide phosphate). By blocking the HMGR enzyme they inhibit the synthesis of cholesterol via the mevalonate pathway. The end result is lower LDL (Low Density Lipoprotein), TG (Triglycerides) and total cholesterol levels as well as increased HDL (High Density Lipoprotein) levels in serum). The ideal statin should have the following properties: One of the main design objectives of statin design is the selective inhibition of HMGR in the liver, as cholesterol synthesis in non-hepatic cells
Comedown (drugs) Comedown (drugs) Comedown or crashing is a phase of drug withdrawal that involves the deterioration in mood and energy that occurs when a psychoactive drug, typically a stimulant, clears from the blood. The improvement and deterioration of mood (euphoria and dysphoria) are represented in the cognitive schema as high and low elevations; thus, after the drug has "elevated" the mood (a state known as a high), there follows a period of "coming back down," which often has a distinct character from withdrawal in stimulants. Generally, a comedown ("down", "low", sometimes "crash") can happen to anyone as a transient symptom, but