Minaprine targets monoamine oxidase A (MAO-A) and serotonin 5-HT2A receptors. As a reversible inhibitor of MAO-A, minaprine increases the levels of monoamine neurotransmitters such as serotonin, norepinephrine, and dopamine in the brain. Minaprine also acts as a serotonin (5-HT2A) receptor antagonist. It has a weak inhibition on acetylcholinesterase. The compound's mechanism of action involves both MAO-A inhibition and 5-HT2A receptor antagonism, which contribute to its antidepressant effects. Minaprine itself is a weak inhibitor of MAO-A in vitro, with evidence strongly suggesting that its in vivo activity is mediated by one or more active metabolites. In vivo, minaprine (acute doses) increases 5-HT, decreases 5-HIAA levels in various brain areas and weakly and reversibly inhibits type A MAO.

In vitro, minaprine is a weak inhibitor of MAO-A, with evidence suggesting that its in vivo activity is mediated by active metabolites. The compound also has a weak inhibition on acetylcholinesterase. In receptor binding assays, minaprine shows affinity for 5-HT2A receptors. The compound's effects on monoamine oxidase activity can be measured in vitro using enzyme preparations, where minaprine shows reversible inhibition of MAO-A. Minaprine's in vitro activity is consistent with its antidepressant effects. The compound's effects on cell viability and proliferation can be assessed in various cell types. Minaprine itself is a weak inhibitor of MAO-A in vitro.

In vivo, minaprine demonstrates antidepressant activity in various animal models and in clinical use. In vivo, minaprine (acute doses) increases 5-HT, decreases 5-HIAA levels in various brain areas and weakly and reversibly inhibits type A MAO; subacute treatments lead to a decrease in the number of 5-HT1 and 5-HT2 receptors. The compound has been reported to be relatively free of cardiotoxicity, drowsiness, and weight gain. Minaprine is a reversible inhibitor of MAO-A; weakly inhibits acetylcholinesterase; an antidepressant for treatment of depression. The compound's in vivo efficacy supports its use as an antidepressant. Minaprine is a psychotropic drug with antidepressant and nootropic properties.

In vitro enzyme assays for minaprine typically measure MAO-A inhibition. The enzyme MAO-A is incubated with minaprine at various concentrations and a substrate such as kynuramine or serotonin. The production of the deaminated metabolite is measured by spectrophotometry or HPLC. The IC₅₀ is calculated from the dose-response curve. For studies investigating the mechanism of inhibition, the reversibility of inhibition is assessed by dialysis or dilution experiments. For acetylcholinesterase inhibition, similar assays are performed using acetylthiocholine as substrate and measuring the production of thiocholine. For 5-HT2A receptor binding, radioligand displacement assays are performed using [³H]-ketanserin.

In vitro cellular assays for minaprine typically employ cell lines expressing MAO-A, 5-HT2A receptors, or neuronal cells. For studies investigating MAO-A inhibition, cells are treated with minaprine, and monoamine oxidase activity is measured. For studies investigating 5-HT2A receptor antagonism, cells expressing the receptor are treated with minaprine in the presence or absence of serotonin, and downstream signaling such as calcium flux is measured. For studies investigating the compound's effects on neurotransmitter levels, neuronal cells are treated with minaprine, and neurotransmitter release or metabolism is measured by HPLC. The compound's effects on cell viability and proliferation can be assessed using standard cytotoxicity assays.

In vivo animal experiments for minaprine employ models of depression and other behavioral disorders. For antidepressant studies, rodents are administered minaprine orally or intraperitoneally, and behavioral tests such as the forced swim test, tail suspension test, or open field test are performed. For studies investigating the mechanism of action, brain tissue is collected for neurochemical analysis to measure neurotransmitter levels and MAO activity. For studies investigating the compound's effects on cognition, learning and memory tests may be performed. Dosing regimens vary depending on the experimental objectives, with acute studies using single doses and chronic studies using repeated daily administration.

Metabolism / Metabolites
The liver. Cytochrome P450 2D is responsible for the 4-hydroxylation of mirtazapine, producing 4-hydroxymirtazapine. Known human metabolites of mirtazapine include 4-hydroxymirtazapine.
The pharmacokinetic properties of minaprine have been characterized in preclinical and clinical studies. Minaprine has a molecular weight of 298.3828 and a molecular formula of C₁₇H₂₂N₄O. The compound is absorbed following oral administration and distributed throughout the body, including the brain. Minaprine is metabolized in the liver, and its metabolites may contribute to its pharmacological activity. The compound's elimination half-life and bioavailability have been characterized. Minaprine has been reported to be relatively free of cardiotoxicity, drowsiness, and weight gain. However, detailed pharmacokinetic data for minaprine is limited in the available literature.

The toxicity profile of minaprine is favorable compared to other antidepressants. The compound has been reported to be relatively free of cardiotoxicity, drowsiness, and weight gain. Common adverse effects may include gastrointestinal disturbances, headache, or insomnia. The compound should be used with caution in patients with a history of seizures or liver disease. Minaprine is a reversible inhibitor of MAO-A, and its use may be associated with serotonin syndrome when combined with other serotonergic agents. The compound's safety in pregnancy and lactation has not been established, and its use should be guided by clinical judgment.

[1]. Effect of the antidepressant minaprine on both forms of monoamine oxidase in the rat. Biochem Pharmacol. 1986 Mar 15;35(6):973-8.

[2]. Aminopyridazines as acetylcholinesterase inhibitors. J Med Chem. 1999 Feb 25;42(4):730-41.

Milnapril belongs to the pyridazine, secondary amine, and morpholine classes of compounds. It has multiple effects, including antidepressant, serotonin reuptake inhibitor, dopamine reuptake inhibitor, cholinergic, and anti-Parkinson's disease drug. Milnapril is a psychotropic drug that has been proven effective in treating various depressive symptoms. Like most antidepressants, milnapril antagonizes behavioral hopelessness. Milnapril is an aminophenylpyridazine antidepressant, and its incidence of cardiotoxicity, drowsiness, and weight gain has been reported to be relatively low. Drug Indications: For the treatment of depression. Mechanism of Action: Milnapril binds to serotonin type 2 receptors and dopamine D1 and D2 receptors. It also binds to the serotonin reuptake pump. Therefore, milnapril blocks the reuptake of dopamine and serotonin. It also has mild cholinergic agonist effects. Therefore, it may simultaneously have mood-enhancing and brain-development-promoting effects. It also functions as a reversible inhibitor of monoamine oxidase A (MAO-A) (RIMA). Furthermore, it has been found to inhibit acetylcholinesterase.

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Pharmacodynamics
Minaprilin is an aminophenylpyridazine antidepressant with reportedly relatively low rates of cardiotoxicity, drowsiness, and weight gain. Similar to other antidepressants, mirtazaprilin attenuates the function of β-adrenergic receptors. Studies have also shown that mirtazaprilin improves memory consolidation, and repeated administration enhances this effect. Furthermore, mirtazaprilin's effect on memory consolidation is related to its dopaminergic activity.
Minaprine is an aminophenylpyridazine antidepressant that is a reversible inhibitor of MAO-A and a serotonin (5-HT2A) receptor antagonist. It also has a weak inhibition on acetylcholinesterase. Minaprine is an antidepressant compound for the treatment of depression. It is a psychotropic drug with antidepressant and nootropic properties. Minaprine has been reported to be relatively free of cardiotoxicity, drowsiness, and weight gain. In vivo, minaprine increases 5-HT and decreases 5-HIAA levels in various brain areas and weakly and reversibly inhibits type A MAO. Minaprine has a molecular weight of 298.3828 and a molecular formula of C₁₇H₂₂N₄O. It is also known as Minaprinum and Minaprina.

C17H22N4O

298.38278

298.179

25905-77-5

Minaprine dihydrochloride;25953-17-7

4199

Typically exists as solid at room temperature

1.156g/cm3

531.2ºC at 760 mmHg

122°

275.1ºC

2.29E-11mmHg at 25°C

1.595

3.811

1

5

5

22

316

0

CC1=CC(C2=CC=CC=C2)=NN=C1NCCN3CCOCC3

LDMWSLGGVTVJPG-UHFFFAOYSA-N

InChI=1S/C17H22N4O/c1-14-13-16(15-5-3-2-4-6-15)19-20-17(14)18-7-8-21-9-11-22-12-10-21/h2-6,13H,7-12H2,1H3,(H,18,20)

4-methyl-N-(2-morpholin-4-ylethyl)-6-phenylpyridazin-3-amine

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)

DMSO : ≥ 35 mg/mL (~117.30 mM)

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.)