Molindone Explained

Molindone, sold under the brand name Moban, is an antipsychotic which is used in the United States in the treatment of schizophrenia.[1] [2] It works by blocking the effects of dopamine in the brain, leading to diminished symptoms of psychosis. It is rapidly absorbed when taken orally.

It is sometimes described as a typical antipsychotic,[3] and sometimes described as an atypical antipsychotic.[4]

Molindone was discontinued by its original supplier, Endo Pharmaceuticals, on January 13, 2010.[5]

Availability and marketing in the USA

After having been produced and subsequently discontinued by Core Pharma in 2015–2017, molindone is available again from Epic Pharma effective December, 2018.[6]

Adverse effects

See main article: Typical antipsychotic.

The side effect profile of molindone is similar to that of other typical antipsychotics. Unlike most antipsychotics, however, molindone use is associated with weight loss.[4] [7]

Chemistry

Synthesis

Condensation of oximinoketone 2 (from nitrosation of 3-pentanone), with cyclohexane-1,3-dione (1) in the presence of zinc and acetic acid leads directly to the partly reduced indole derivative 6. The transformation may be rationalized by assuming as the first step, reduction of 2 to the corresponding α-aminoketone. Conjugate addition of the amine to 1 followed by elimination of hydroxide (as water) would give ene-aminoketone 3. This enamine may be assumed to be in tautomeric equilibrium with imine 4. Aldol condensation of the side chain carbonyl group with the doubly activated ring methylene group would then result in cyclization to pyrrole 5; simple tautomeric transformation would then give the observed product. Mannich reaction of 6 with formaldehyde and morpholine gives the tranquilizer molindone (7).

See also

Notes and References

  1. Web site: molindone . F.A. Davis Company .
  2. Web site: Molindone.
  3. Aparasu RR, Jano E, Johnson ML, Chen H . Hospitalization risk associated with typical and atypical antipsychotic use in community-dwelling elderly patients . Am J Geriatr Pharmacother . 6 . 4 . 198–204 . October 2008 . 19028375 . 10.1016/j.amjopharm.2008.10.003 .
  4. Bagnall A, Fenton M, Kleijnen J, Lewis R . Molindone for schizophrenia and severe mental illness . Cochrane Database Syst Rev . 1 . CD002083 . 2007 . 17253473 . 10.1002/14651858.CD002083.pub2 . Bagnall AM .
  5. Web site: Drugs to be Discontinued . www.fda.gov . dead . https://web.archive.org/web/20090603081808/http://www.fda.gov/Drugs/DrugSafety/DrugShortages/ucm050794.htm . 2009-06-03.
  6. Web site: NEWS. www.epic-pharma.com. 2018-12-12.
  7. Allison DB, Mentore JL, Heo M, Chandler LP, Cappelleri JC, Infante MC, Weiden PJ . Antipsychotic-induced weight gain: a comprehensive research synthesis . The American Journal of Psychiatry . 156 . 11 . 1686–1696 . November 1999 . 10553730 . 10.1176/ajp.156.11.1686 . 38635470 .