Molindone

Molindone (Moban) is a therapeutic antipsychotic, used in the treatment of schizophrenia. It works by blocking the effects of dopamine in the brain, leading to diminished psychoses. It is rapidly absorbed when taken orally.

It is sometimes described as a typical antipsychotic, and sometimes described as an atypical antipsychotic.

Molindone was discontinued by its sole supplier, Endo Pharmaceuticals, on January 13, 2010.

Adverse effects

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.

Synthesis

Condensation of oximinoketone 2 (from nitrosation of 3-pentanone), with 1,3-cyclohexanedione (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 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).