Antipsychotics molindone

Most conventional antipsychotics are associated with a dose-depen-dent risk of a lowered seizure threshold, although the incidence of seizures with most of these drugs is quite small (Devinsky et al. 1991). Of all the conventional antipsychotics, molindone and fluphenazine have been shown most consistently to have the lowest potential for this side effect (ltd and Soldatos 1980 Ohver et al. 1982). The atypical antipsychotic clozapine is associated with a dose-dependent risk of seizure. 

QF-0400B, typical antipsychotic molindone, typical antipsychotic... 

If a change in antipsychotic therapy is required, risperidone, molindone, thioridazine, haloperidol, pimozide, trifluoperazine, and fluphenazine may be considered. 

Whatever the underlying causes may be, neuroleptic medications are the most effective treatment for schizophrenia. All antipsychotic medications have some form of dopamine receptor antagonism and they are distinguished by their chemical class. The phenothiazines include chlorpromazine (Thorazine), thioridazine (Mellaril), mesoridazine (Serentil), trifluoperazine (Stelazine), fluphenazine (Prolixin), and prochlorperazine (Compazine). The thioxanthenes include chlorprohixine (Taractan) and thiothixene (Navane). Butyrophenones are represented by haloperidol (Haldol). Loxapine (Loxitane) is a dibenzoxapine, and molindone (Moban) is a dihydroindolone. 

Molindone (Moban). Molindone is another of the medinm potency antipsychotics. There are two featnres that set it apart. First, it is less prone to cansing weight gain than other antipsychotics. As a result, it is sometimes preferred for obese schizophrenia patients. Second, although typical antipsychotics do not necessarily cause seizures, they may make them more likely to occur in people who are already prone to seizures. There is some evidence to suggest that molindone may be the least likely antipsychotic to increase the vulnerability to seizures. For this reason, molindone is frequently used to treat patients with schizophrenia who also have epilepsy. 

Molindone is a more active antipsychotic than chloropromzine. Its sedative effect is less expressed. Side effects are also expressed less than with powerful neuroleptics. It facilitates the reduction of spontaneous movements and aggressiveness, and is used for treatment of psychotic disturbances, particularly in cases of chronic and severe schizophrenia. A synonym of this drug is moban. 

Pimozide and molindone are typical antipsychotic drugs. There is no significant difference in efficacy between these newer typical and the older typical... 

The dibenzoxapine loxapine and the indolone molindone are also used as antipsychotics. 

OFFICIAL NAMES Major tranquilizers (neuroleptics/antipsychotics) Chlorpromazine (Thorazine) chlorprothixene (Taractan) clozaril (Clozapine) fluphenazine (Permitil, Prolixin) haloperidol (Haldol) loxapine (Daxolin, Loxitane) mesoridazine (Serentil) molindone (Lidone,... 

In our model, we have indicated that atypical antipsychotics (12) (sulpiride, metoclopramide, molindone, and Ro 22-1319) differ from classical neuroleptics (tricyclics, butyrophenones, butaclamol, diphenyl-piperidines) by lacking a lipophilic functional group on the basic nitrogen that could extend into the auxiliary binding site identified in our model. The absence of this lipophilic functionality may now be stated to be the characteristic which distinguishes selective D-2 dopamine receptor antagonists from non-selective antagonists. 

Other, chemically distinct dopamine blockers were then developed, such as thiothixene, haloperidol, loxapine, molindone, and pimozide. All of these antipsychotics are potent dopamine blockers and collectively were called neuroleptics because they inadvertently cause certain neurological side effects (discussed below). More recently, atypical antipsychotic medications have been developed (clozapine and risperidone), which are effective antipsychotics yet are weak dopamine blockers and cause minimal neurological side effects. This group is discussed separately below. 

Molindone Hydrochloriele. Molindone hydrochloride. 3-ethyl-6.7-dihydro-2-mcthyl-5-morpholinomcthyl)indole-4(S//)-one monohydrochloride (Mohan), is about as potent an antipsychotic as trifluoperazine. Overall, side effects resemble those of (he phenothiazines. 

The clinical pharmacodynamics and pharmacokinetics of molindone (91) have been reviewed (525). The drug is reputed to be rapidly absorbed after oral administration and rapidly metabolized. Only 2-3% of the unchanged drug can be recovered in the urine and feces. Molindone has a very short half-like (1.5-2 h) and is 1.5-1.7 times more bioavailable after intramuscular, rather than oral, administration (526). Molindone is less lipophilic than most antipsychotic drugs and has a lower fraction (around 75%)that is bound to proteins in the plasma (527).Clinical studies indicate that the antipsychotic effectiveness of molindone lasts more than 24 h (525,528,5291, suggesting that one or more active metabolites may contribute to its actions in vivo. 

A series of 6-aminoalkyltetrahydroindol-4-ones related to molindone (91) show potent affinities for D, and 5-HT receptors (610). Molindone exhibits many similarities to typical neuroleptics, including Dg antagonism, antipsychotic efficacy, and EPS (611). Zotepine (136) is a potent D, and 5-HT antagonist with high affinity for the 5-HT, receptor. 

The present view is that D-2, as a high-affinity species, represents the presynaptic autoreceptor in the CNS. The low-affinity D-2 receptor, then, is postsynaptic. D2 receptors are not coupled to c-AMP as a secondary messenger. Their mass is estimated as 136,700 daltons. The structural variety of D-2 antagonists varies considerably and includes many clinically important groups of antipsychotic drugs the phenothiazine tranquilizers and several of their bioisosteres (the butyrophenones), a dibenzodiazepine (clozapine), the indole derivative molindone, and a benzamide (sulpiride), all to be discussed later. The ergot alkaloids represent D-2 agonists. 

The dihydroindolone molindone, though structurally different from the phenothiazine and butyrophenones, shares most of their antipsychotic properties and side effects. Its clinical effects resemble those of the piperazine phenothiazines. The drug s specific advantages, if any, are not readily apparent. 

Several newer drugs of varied beterocyclic structure are also effeetive in schizophrenia, ineluding elozapine, loxapine, olanzapine, molindone, pimozide, risperidone, quetiapine, and sertindole. In some cases, these atypical antipsychotic drugs have proved to be more effective and less toxic than the older drugs. However, they are much more eostly than standard drugs, most of whieh are preseribed generically. 

The concurrent use of bromocriptine with antipsychotics can be successful. However, one report describes the re-emei ence of schizophrenic symptoms in a patient when bromocriptine was added to treatment with molindone and imipramine. Another case reports a rise in prolactin levels and deterioration of vision when thioridazine was given with bromocriptine. 

Additional studies on oxypertine (XIX) indicate that the major advantage of this compound is its mood elevating and stimulant properties in schizophrenics where apathy is a major problem.In a double blind study with chlorpromazine oxypertine was judged to be of value in the treatment of chronic schizophrenia, In two clinical studies, molindone (XX) was shown to be equal to trifluoperazine as an antipsychotic but antidepressant properties were not noted at the dosage used. "... 

The reported contribution of pyrrole nuclei to the sedative action of ketone derivatives encouraged the synthesis of relatives of 4 in which the benzene ring was replaced by pyrrole. Molindone (EN-1733, 5), which is two to three times as potent as chlorpromazine in the rat, was among the most active and least toxic of the potential antipsychotic agents of the new series Aspects of its profile suggestive of antidepressant activity have been reported Two published studies describe the effective antipsychotic action of molindone in chronic schizophrenics. Unusual euphoria was noted in some patients. 

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