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Meprobamate — marketed as ''Miltown'' by Wallace Laboratories and ''Equanil'' by Wyeth, among others — is a carbamate derivative used as an anxiolytic drug. It was the best-selling minor tranquilizer for a time, but has largely been replaced by the benzodiazepines due to their wider therapeutic index (lower toxicity) and lower incidence of serious side effects. ==History== In the mid-1940s, Frank Milan Berger was working in a laboratory of a British drug company, looking for a preservative for penicillin, when he noticed that a compound called mephenesin had a sedative effect in laboratory rodents. Berger subsequently referred to this sedating or “tranquilizing” effect in a now-historic article, published by ''The British Journal of Pharmacology'' in 1946. However, there were three major drawbacks to the use of mephenesin as a tranquilizer: a very short duration of action, greater effect on the spinal cord than on the brain, and a weak activity. In May 1950, after moving to Carter Products in New Jersey, Berger and a chemist, Bernard John Ludwig, synthesized a chemically related tranquilizing compound, meprobamate, that was able to overcome these three drawbacks. Wallace Laboratories, a subsidiary of Carter Products, bought the license and named their new product "Miltown" after the borough of Milltown in New Jersey. Launched in 1955, it rapidly became the first blockbuster psychotropic drug in American history, becoming popular in Hollywood and gaining notoriety for its seemingly miraculous effects. It has since been marketed under more than 100 trade names, from ''Amepromat'' through ''Quivet'' to ''Zirpon''.〔(http://webbook.nist.gov/cgi/cbook.cgi?ID=57-53-4 )〕 A December 1955 study of 101 patients at the Mississippi State Hospital in Whitfield, Mississippi, found meprobamate useful in the alleviation of "mental symptoms." Three percent of the patients made a complete recovery, 29% were greatly improved, and 50% were somewhat better. Eighteen percent realized little change. Self-destructive patients became cooperative and calmer, and experienced a resumption of logical thinking. In 50% of the cases relaxation brought about more favorable sleep habits. Hydrotherapy and all types of shock treatment were halted.〔"New Hope Arises On Cancer Serum", ''The New York Times'', December 28, 1955, Page 21.〕 Meprobamate was found to help in the treatment of alcoholics by 1956. By 1957, over 36 million prescriptions had been filled for meprobamate in the US alone, a billion pills had been manufactured, and it accounted for fully a third of all prescriptions written. Berger, clinical director of Wallace Laboratories (who died on March 16, 2008, aged 94), described it as a relaxant of the central nervous system, whereas other tranquilizers suppressed it. A University of Michigan study found that meprobamate affected driving skills. Though patients reported being able to relax more easily, meprobamate did not completely alleviate their tense feelings. The disclosures came at a special scientific meeting at the Barbizon Plaza Hotel in New York City, at which Aldous Huxley addressed an evening session. He predicted the development of many chemicals "capable of changing the quality of human consciousness", in the next few years. In January 1960, Carter Products, Inc. and American Home Products Corporation (which marketed meprobamate as ''Equanil'') were charged with having conspired to monopolize the market in mild tranquilizers. It was revealed that the sale of meprobamate earned $40,000,000 for the defendants. Of this amount American Home Products accounted for approximately 2/3 and Carter about 1/3. The U.S. government sought an order mandating that Carter make its meprobamate patent available at no charge to any company desiring to use it.〔 〕 In April 1965, meprobamate was removed from the list of tranquilizers when experts ruled that the drug was a sedative instead. The ''U.S. Pharmacopoeia'' published the ruling. At the same time the ''Medical Letter'' disclosed that meprobamate could be addictive at dosage levels not much above recommended.〔 〕 In December 1967, meprobamate was placed under abuse control amendments to the Food, Drug and Cosmetic Act. Records on production and distribution were required to be kept. Limits were placed on prescription duration and refills.〔 〕 Production continued throughout the 1960s, but by 1970 meprobamate was listed as a controlled substance after it was discovered to cause physical and psychological dependence. On January 19, 2012, the European Medicines Agency withdrew marketing authorization in the European Union for all medicines containing meprobamate, "due to serious side effects seen with the medicine." The Agency’s Committee for Medicinal Products for Human Use (CHMP) "concluded that the benefits of meprobamate do not outweigh its risks."〔 (【引用サイトリンク】 title=Questions and answers on the suspension of the marketing authorisations for oral meprobamate-containing medicines ) 〕 In October 2013, Canada also withdrew marketing authorization.〔Health Canada. (282 MEP (meprobamate-containing medicine) - Market Withdrawal, Effective October 28, 2013 - For Health Professionals )〕 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「Meprobamate」の詳細全文を読む スポンサード リンク
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