Absorption, Distribution and Excretion
Rapidly absorbed from the gastrointestinal tract following oral administration.
Human metabolic studies show molindone to be rapidly absorbed and metabolized when given orally. There are 36 recognized metabolites with less than 2-3% unmetabolized molindone being excreted in urine and feces.
REACHES PEAK BLOOD LEVELS WITHIN 1 HR AFTER ORAL ADMIN.

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Metabolism / Metabolites
Most likely hepatic. 36 metabolites have been recognized, some of which may be active.

Hepatotoxicity
Liver test abnormalities have been reported to occur in a small proportion of patients on long term therapy with molindone, but elevations are uncommonly above 3 times the upper limit of normal. The aminotransferase abnormalities are usually mild, asymptomatic and transient, reversing even with continuation of medication. Instances of clinically apparent acute liver injury have been reported due to molindone, but are rare. The onset of injury is within 4 to 8 weeks, and the pattern of serum enzyme elevations is typically hepatocellular. Jaundice is uncommon and most cases are self-limited and mild. Immunoallergic features and autoantibody formation are not typical.
Likelihood score: D (possible, rare cause of clinically apparent liver injury).

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Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Because there is no published experience with molindone during breastfeeding, other antipsychotic agents are preferred.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
Galactorrhea has been reported with molindone. Hyperprolactinemia appears to be the cause of the galactorrhea. The hyperprolactinemia is caused by the drug's dopamine-blocking action in the tuberoinfundibular pathway. The maternal prolactin level in a mother with established lactation may not affect her ability to breastfeed.

Molindone is a member of indoles.
An indole derivative effective in schizophrenia and other psychoses and possibly useful in the treatment of the aggressive type of undersocialized conduct disorder. Molindone has much lower affinity for D2 receptors than most antipsychotic agents and has a relatively low affinity for D1 receptors. It has only low to moderate affinity for cholinergic and alpha-adrenergic receptors. Some electrophysiologic data from animals indicate that molindone has certain characteristics that resemble those of clozapine. (From AMA Drug Evaluations Annual, 1994, p283)
Molindone is a Typical Antipsychotic.
Molindone is a conventional antipsychotic agent used in the therapy of schizophrenia. Molindone therapy is commonly associated with minor serum aminotransferase elevations but has rarely been linked to cases of clinically apparent acute liver injury.
An indole derivative effective in schizophrenia and other psychoses and possibly useful in the treatment of the aggressive type of undersocialized conduct disorder. Molindone has much lower affinity for D2 receptors than most antipsychotic agents and has a relatively low affinity for D1 receptors. It has only low to moderate affinity for cholinergic and alpha-adrenergic receptors. Some electrophysiologic data from animals indicate that molindone has certain characteristics that resemble those of CLOZAPINE. (From AMA Drug Evaluations Annual, 1994, p283)
See also: Molindone Hydrochloride (has salt form).

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Drug Indication
Molindone is used for the management of the manifestations of psychotic disorders.

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Mechanism of Action
The exact mechanism has not been established, however, based on electroencephalogram (EEG) studies, molindone is thought to act by occupying (antagonizing) dopamine (D2) receptor sites in the reticular limbic systems in the brain, thus decreasing dopamine activity. Decreased dopamine activity results in decreased physiological effects normally induced by excessive dopamine stimulation, such as those typically seen in manifestations of psychotic disorders.
INFORMATION IS INADEQUATE TO DETERMINE SPECIFIC ACTIONS OF MOLINDONE...
THIS ANTIPSYCHOTIC AGENT IS A DIHYDROINDOLONE DERIV. IT IS NOT CHEM RELATED TO PHENOTHIAZINES, BUTYROPHENONES OR THIOXANTHENES, BUT PHARMACOLOGIC ACTIONS ARE SIMILAR TO THOSE OF PIPERAZINE PHENOTHIAZINES.

276.37396

276.184

7416-34-4

Molindone hydrochloride;15622-65-8;Molindone-d8;1189805-13-7

23897

CRYSTALS

1.14 g/cm3

462.9ºC at 760 mmHg

180 - 181ºC

233.7ºC

1.559

1.9

1

3

3

20

354

0

O=C1C(CN2CCOCC2)CCc2c1c(CC)c(C)[nH]2

KLPWJLBORRMFGK-UHFFFAOYSA-N

InChI=1S/C16H24N2O2/c1-3-13-11(2)17-14-5-4-12(16(19)15(13)14)10-18-6-8-20-9-7-18/h12,17H,3-10H2,1-2H3

3-ethyl-2-methyl-5-(morpholin-4-ylmethyl)-1,5,6,7-tetrahydroindol-4-one

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)