Parker & Waichman, LLP Attorneys at Law Reminyl Information Guide
The Case Against Reminyl:
Data from two clinical trials indicated that people taking Reminyl (generic: galantamine) have a much higher death rate than those taking Manufacturer: a placebo. Reminyl is an Alzheimer's disease drug. The review was announced on 1/21/05 by Johnson & Johnson, which said it's in Johnson & Johnson discussions with the Food and Drug Administration.
Generic Name: The trials, involved approximately 2,000 patients in 16 countries. were Galantamine looking if Reminyl could be used to treat mild cognitive impairment, a form of memory loss that is often associated with Alzheimer's. Reminyl Date Approved: is approved in 69 countries as a treatment for mild to moderate June 22, 2001 Alzheimer's but not for mild cognitive impairment. In the trials, which lasted two years, 15 patients taking Reminyl died compared with 5 Status: taking the placebo. On the market The announcement comes at a time of heightened concern over the safety of widely used drugs after the withdrawal from the market of Approved Uses: Merck's pain reliever, Vioxx, which studies indicated posed an Alzheimers increased risk of heart attacks and strokes.
Off Label Uses: Johnson & Johnson responded by saying that the overall number of Mild cognitive impairment deaths in the trials was low for the elderly population in the trial and that the incidence of serious side effects was the same for patients getting Serious Side Effects: the drug and the placebo. Also, it said, the investigators in the trials had Higher death rate not thought the drug caused any of the deaths.
Related Topics: Reminyl was approved on the basis of six-month studies but the mild cognitive impairment trials lasted two years, increasing their chances of Defective Drugs detecting side effects. Nevertheless, the Johnson & Johnson analysis said the excess of deaths in the mild cognitive impairment trials was evident by six months, while no such excess was seen in the Alzheimer's trials.
Reminyl was developed with Shire Pharmaceuticals of Britain. Sales for Johnson & Johnson are estimated at about $200 million a year. Public Citizen, the watchdog group, recommends against using Reminyl or other drugs in its class, saying they have minimal benefit and the effectiveness and safety of taking them longer than six months is not known, according to Sidney Wolfe, director of health research.
If you or a loved one has been injured by Reminyl, Parker & Waichman, LLP will evaluate your case for free. Click here for a free, no obligation, case evaluation.
Reminyl (Galantamine) From Wikipedia, the free encyclopedia.
Galantamine (Razadyne®) is a medication used in the treatment of Alzheimer's disease.
Galantamine is mostly used as hydrobromide salt. It is a centrally acting reversible cholinesterase inhibitor in the same class as donepezil. Galantamine has a much shorter half life than donepezil (there is a newer prolonged release version available in 2004) and it also has more nicotinic receptor activity and is potentially more stimulating but also probably because of this activity tends to cause worse gastrointestinal side effects.
The total synthesis of Galanthamine (Trost 2005) is described as follows (see scheme 1): the sequence starts by bromination by electrophilic aromatic substitution of isovanillin 1 to bromophenol 2, then by synthesis of the second intermediate 5 by reacting dialdehyde 3 in a coupled aldol reaction and Horner-Wadsworth-Emmons reaction with trimethyl phosphonoacetate 4. The hydroxyl group is activated as a leaving group by acetylation with trichloroethyl carbonate (Troc) to 6. Next a enantioselective Trost AAA reaction takes place between bromophenol 2 and carbonate 6 to the allyl ether 7. Next the aldehyde group is protected as an acetal in 8 and this step enables the to organic reduction of the ester group to the alcohol 9 with DIBAH and subsequent conversion of this alcohol to a nitrile by nucleophilic displacement to 10 followed by aldehyde deprotection to 11. The intramolecular Heck reaction to 12 creates the dihydrofuran ring. Allylic oxidation by selenium dioxide provides allylic alcohol 13 with the correct stereochemistry. The aldehyde reacts with methylamine to the imine 14 and reduction of the imine and nitrile by DIBAL-H leading to ring-closure to the hemi- aminal 15 (not isolated) followed by acid quenching gives the alcohol 16. In the final step this alcohol group is reduced to give Galanthamine 17 together with 6% of the epi isomer 18.
References
^ Divergent Enantioselective Synthesis of (-)-Galanthamine and (-)-Morphine Barry M. Trost, Weiping Tang, and F. Dean Toste J. Am. Chem. Soc.; 2005; 127(42) pp 14785 - 14803; (Article) DOI: 10.1021/ja054449+ Abstract Scheme 1. Trost 2005 Galanthamine total synthesis:a bromine, sodium acetate, acetic acid, iron, rt b potassium carbonate, 2days c Troc-Cl, DMAP, Pyridine, dichloromethane d palladium,Trost ligand, triethylamine, dichloromethane e 1.5 mol % TsOH, CH(OMe)3, methanol f DIBAL-H, toluene, -78 °C, 1 hr g triphenylphosphine, acetonecyanohydrin, DIAD, diethyl ether h 2.20 mol % TsOH, THF, water i 15 mol % Palladium(II) acetate, 15 mol% dppp, 3 eq. Ag2CO3, toluene, 107 °C j selenium dioxide disodium hydrogen phosphate dioxane, 150 °C 3 hrs k methylamine ,methanol l 4 eq. DIBAL-H, m aqueous NaH2PO4 n
If you or a loved one has been injured by Reminyl, Parker & Waichman, LLP will evaluate your case for free. Click here for a free, no obligation, case evaluation.