Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0917801 (insomnia)
 10,606 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of lovastatin, simvastatin and pravastatin, which are competitive inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, was tested on PGD synthase purified to apparent homogeneity from the rat brain. Lovastatin and simvastatin, which reportedly cause insomnia in vivo, inhibited the PGD synthase activity dose-dependently and showed an IC50 value of 100 and 75 microM, respectively. On the other hand, pravastatin, which does not cause insomnia, showed no significant effect at 100 microM and only a slight effect up to 500 microM.
 ...
PMID:Inhibition of rat brain prostaglandin D synthase by 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors. 212 71

New information on the tolerability of lovastatin has emerged from an ongoing study of long-term therapy; preliminary results from a large, 48-week clinical trial; and spontaneous reports of adverse events observed during prescription use of the drug in the United States. As of June 1989, 744 patients had received lovastatin for an average duration of 3.6 years in the long-term study. Drug-attributable adverse events necessitated withdrawal of 17 patients (2.3%) from the study. These adverse effects were asymptomatic elevations of transaminases (10), skin rash (3), gastrointestinal symptoms (2), myopathy (1) and insomnia (1). No effect of lovastatin on the human lens was observed. In the 48-week study, 8,245 patients were randomized into 5 equal groups to receive placebo or lovastatin 20 or 40 mg once or twice daily on a double-blind basis. Only 3 cases of myopathy were observed, all in patients taking lovastatin 40 mg twice daily. The incidence of withdrawal from the study because of raised transaminases was approximately 0.1% in the placebo group vs 0.1, 0.7, 0.6 and 1.5% in patients taking lovastatin in doses of 20 mg once daily, 40 mg once daily, 20 mg twice daily and 40 mg twice daily, respectively. Lovastatin has been available in the United States since September 1987. By June 1989, the drug had been prescribed for approximately 1 million patients. Drug-attributable adverse events not observed in clinical trials (such as hypersensitivity reactions and symptomatic hepatitis) have been reported, but the incidence of each appears to be extremely low.
 ...
PMID:Clinical experience with lovastatin. 218 Feb 68

The efficacy of lovastatin, a potent inhibitor of HMG CoA reductase, has been established by numerous studies. At doses of 40 mg administered twice daily, lovastatin produces a mean reduction in total plasma cholesterol of 33%, attributable to a reduction in low-density lipoprotein cholesterol of 41%. The drug also produces a mean increase in high-density lipoprotein cholesterol of 9%, and a reduction in the high- and low-density lipoprotein cholesterol ratio of 44%. The serious reported adverse effects of lovastatin are myopathy (0.5%) and asymptomatic but marked and persistent increases in transaminases (1.9%). Both are reversible when therapy is discontinued. Myopathy has occurred mainly in patients with complicated histories who were receiving concomitant therapy with immunosuppressive drugs, gemfibrozil or niacin. In an ongoing long-term safety study, 744 patients have received lovastatin for an average duration of 2.5 years up to March 1988. Fifteen patients (2.0%) have been withdrawn because of drug-attributable adverse events: raised transaminases (9), skin rash (2), gastrointestinal symptoms (2), myopathy (1) and insomnia (1). No effect of the drug on the human lens has been observed up to the date mentioned above. Lovastatin has been available in the United States since September 1987. By March 1988, the drug had been prescribed for approximately 250,000 patients. This clinical experience has confirmed the tolerability observed in clinical trials. The good adverse-effect profile of lovastatin is thus now supported both by a substantial body of data in patients treated for over 2 years in clinical trials, and by experience in clinical use with a large number of patients since the drug has been available for prescription.
 ...
PMID:Efficacy and long-term adverse effect pattern of lovastatin. 305 21

We have evaluated the hypolipidemic effects of mevinolin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, the rate-limiting enzyme in cholesterol biosynthesis in 13 patients with heterozygous familial hypercholesterolemia (FH). Patients were maintained on a low-cholesterol diet and received sequentially increasing doses of 5, 10, 20, and 40 mg of mevinolin twice daily for a period of 1 mo on each dose. Plasma concentrations of low density lipoprotein cholesterol decreased by 19.8% on the 5 mg twice daily dose (P less than 0.05 vs. base line), 28.4% on 10 mg of mevinolin twice daily (P less than 0.05 vs. 5 mg twice daily), 35% on 20 mg of mevinolin twice daily (P less than 0.05 vs. 10 mg twice daily), and 37.7% on 40 mg of mevinolin twice daily (not statistically different from 20 mg twice daily). Concentrations of high density lipoprotein cholesterol remained stable on all doses of mevinolin whereas plasma triglyceride levels fell significantly on the 20 mg (-30.7%) and 40 mg (-34.3%) twice daily doses of mevinolin. Mevinolin was well tolerated and all patients completed the study period. Side effects during the period of study were limited to transient insomnia and headaches in two patients, transient increases in alkaline phosphatase in three patients, and a modest but sustained increase in alkaline phosphatase in a fourth patient. These results indicate that mevinolin is an effective hypolipidemic agent in patients with heterozygous FH but that the optimal doses in these patients are greater than those previously reported in normal volunteers. If long-term safety can be satisfactorily established, mevinolin offers considerable promise in the therapy of heterozygous FH.
 ...
PMID:Hypocholesterolemic effects of mevinolin in patients with heterozygous familial hypercholesterolemia. 656 64