Tybamate Explained

Tybamate (INN; Solacen, Tybatran, Effisax) is an anxiolytic of the carbamate family.^[1] It is a prodrug for meprobamate in the same way as the better known drug carisoprodol. It has liver enzyme inducing effects similar to those of phenobarbital but much weaker.^[2]

As the trade name Tybatran (Robins), it was formerly available in capsules of 125, 250, and 350 mg, taken 3 or 4 times a day for a total daily dosage of 750 mg to 2 g. The plasma half-life of the drug is three hours. At high doses in combination with phenothiazines, it could produce convulsions.^[3]

Synthesis

Catalytic hydrogenation of 2-methyl-2-pentenal (1) gives the aldehyde 2-methylpentanal (2). Treatment with formaldehyde gives a crossed Cannizzaro reaction yielding 2,2-bis(hydroxymethyl)pentane (3). Cyclisation of this diol with diethyl carbonate gives (4), which reacts with ammonia to provide the carbamate (5). Lastly, treatment with butyl isocyanate (6) produces tybamate.^{[4] [5] [6]}

Notes and References

1. Book: Index Nominum 2000: International Drug Directory . January 2000 . Taylor & Francis . 978-3-88763-075-1 . 1077.
2. Segelman FH, Kelton E, Terzi RM, Kucharczyk N, Sofia RD . The comparative potency of phenobarbital and five 1,3-propanediol dicarbamates for hepatic cytochrome P450 induction in rats . Research Communications in Chemical Pathology and Pharmacology . 48 . 3 . 467–70 . June 1985 . 4023427 .
3. Book: 406 . AMA Drug Evaluations . 3rd . 1977 . Pub. Sciences Group . Littleton, Mass. . American Medical Association Dept of Drugs . 978-0-88416-175-2 . 1024170745.
4. 10.1021/ja01156a086 . Some Anticonvulsant Agents Derived from 1,3-Propanediols . 1951 . Ludwig BJ, Piech EC . Journal of the American Chemical Society . 73 . 12 . 5779–5781 .
5. Book: 10.1016/S0099-5428(08)60025-8 . Tybamate . Analytical Profiles of Drug Substances . 1975 . Reisberg P, Kress J, Bodin JI . 4 . 494–515 . 978-0-12-260804-9 .
6. Web site: Tybamate . Pharmaceutical Substances . Thieme . 2024-07-08.