Minaprine dihydrochloride
(Synonyms: 米那卜林二盐酸盐) 目录号 : GC30949
Minaprine二盐酸盐是单胺氧化酶MAO-A可逆性抑制剂，还对乙酰胆碱酯酶有微弱抑制，抗抑郁类化合物。
Cas No.:25953-17-7
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Minaprine 2Hcl is a reversible inhibitor of MAO-A; weakly inhibit acetylcholinesterase; an antidepressant for treatment of depression.
[1]. Kan JP, et al. Effect of the antidepressant minaprine on both forms of monoamine oxidase in the rat. Biochem Pharmacol. 1986 Mar 15;35(6):973-8. [2]. Contreras JM, et al. Aminopyridazines as acetylcholinesterase inhibitors. J Med Chem. 1999 Feb 25;42(4):730-41.
| Cas No. | 25953-17-7 | SDF | |
| 别名 | 米那卜林二盐酸盐 | ||
| Canonical SMILES | [H]Cl.CC1=CC(C2=CC=CC=C2)=NN=C1NCCN3CCOCC3.[H]Cl | ||
| 分子式 | C17H24Cl2N4O | 分子量 | 371.3 |
| 溶解度 | DMSO : ≥ 100 mg/mL (269.32 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.6932 mL | 13.4662 mL | 26.9324 mL |
| 5 mM | 0.5386 mL | 2.6932 mL | 5.3865 mL |
| 10 mM | 0.2693 mL | 1.3466 mL | 2.6932 mL |
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动物数量 | 只 |
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2.
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Cholinomimetic activities of minaprine
The cholinomimetic activities of the antidepressant drug minaprine have been investigated, in vitro and in vivo, in rodents. Minaprine, and its metabolite SR 95070B [3-(2-morpholinoethylamino)-4-methyl-6-(2-hydroxyphenyl) pyridazine hydrochloride] selectively displaced [3H]-pirenzepine from its cortical and hippocampal binding sites, and only weakly inhibited the binding of [3H]-N-methylscopolamine in either the rat cerebellum, heart and salivary glands, or the guinea-pig ileum. In mice, none of these drugs induced the typical cholinergic side-effects up to lethal doses. Minaprine and SR 95070B antagonized rotations induced by an intrastriatal injection of pirenzepine in mice, after intraperitoneal and/or oral administration. Minaprine also antagonized atropine-induced mydriasis in mice. Both minaprine and SR 95070B potentiated the tremorigenic effect of oxotremorine without inducing tremor when injected alone. Finally, minaprine and SR 95070B, after parenteral and/or oral injection, antagonized the scopolamine-induced deficit in passive avoidance learning, and enhanced short-term retention in the social memory test, in rats. The muscarinic agonists arecoline, oxotremorine and RS 86 [2-ethyl-8-methyl-2,8 diazaspiro-4,5 decan-1,3 dion hydrobromide], as well as the acetylcholine esterase inhibitors physostigmine and tacrine were active in most of these models. These results indicate that minaprine, and its metabolite SR 95070B, have cholinomimetic activities which could be, at least in part, mediated by their selective affinity for M1 muscarinic receptors. Thus minaprine could represent a potential useful drug for the treatment of senile dementias and cognitive impairments occurring in elderly people.
Pharmacological evaluation of minaprine dihydrochloride, a new psychotropic drug
Minaprine (3-[2-morpholino-ethlamino]-4-methyl-6-phenyl-pyridazine dihydrochloride; 30038CM; trade name in France: Cantor) is a new psychotropic drug. The therapeutic profile of minaprine differs from that of other known psychotropic agents; in man the drug antagonizes the "inhibitory syndrome" characterized by decreased spontaneous activity, reduction in basic drives, slowed thoughts, feelings of tiredness and social withdrawal. Preliminary clinical trials have indicated that minaprine may also be effective in certain depressive states. This finding prompted us to study the effects of minaprine in animal models for depression. Like most antidepressants minaprine antagonizes behavioral despair, but the effect exhibits a slow onset and maximal activity is reached 24 h after administration. Minaprine also antagonizes reserpine-induced ptosis, this effect has a rapid onset, and is long-lasting. In contrast, minaprine poorly antagonizes reserpine-induced hypothermia. Unlike most antidepressants minaprine does not potentiate yohimbine-induced lethality. Minaprine potently antagonizes prochlorperazine-induced catalepsy in rats and potentiates amphetamine-induced stereotyped behavior, suggesting that the drug may enhance dopaminergic transmission. Finally, minaprine does not antagonize either oxotremorine-induced tremors or physiostigmine-induced lethality. Taken together the results of the present study indicate that minaprine is active on certain, but not all, animal models for depression and suggest the drug may have a potential clinical utility in the treatment of human depressions.
[(3)H]Minaprine binding to membrane preparation from rat brain
The specific binding site of minaprine [3-(2-morpholino-ethylamino)-4-methyl-6-phenyl-pyridazine] in the rat brain was studied. The specific binding site of [(3)H]minaprine was found to be mostly evenly distributed in rat brain. The affinity of [(3)H]minaprine was highest in the hippocampus, with a dissociation constant (K(d)) of 56.3 nM, compared with the affinity in the cerebral cortex and the striatum. The specific [(3)H]minaprine binding on a mg-protein basis was largest in the microsomal fraction. The affinity of [(3)H]minaprine was significantly higher in the synaptosomal fraction compared with the affinity in the mitochondrial and microsomal fractions in the brain. The affinity of [(3)H]minaprine binding was slightly increased by increasing the reaction temperature. A net increase of entropy in [(3)H]minaprine binding was observed, accompanied by a decrease in free energy and a slight increase in enthalpy. Minaprine and an active metabolite of minaprine, 3-(2-morpholino)-4-methyl-6-(4-hydroxyphenyl)-pyridazine (M-3), inhibited [(3)H]minaprine binding. Neurotransmitter-related compounds all failed to inhibit [(3)H]minaprine binding, except phencyclidine, tetraethylammonium (TEA) and 4-aminopyridine. These results suggest that minaprine binds with high affinity to a specific binding site on the synaptic membrane, and that the site is related to a voltage-dependent K(+) channel.
Molecular mechanisms in the action of minaprine
1. Minaprine is a pyridazine derivative endowed with antidepressant activity, however biochemical studies following repeated administrations are still lacking. 2. Rats were administered with minaprine (10 mg/kg i.p.) twice daily for 3 weeks. 3. In minces from the frontal cortex of rats receiving minaprine the NE-induced cAMP accumulation is reduced suggesting that, similarly to other antidepressant treatments, minaprine attenuates the beta-adrenergic receptor function. 4. The selective lesion of the serotonergic axons abolished such attenuation. 5. In synaptic plasma membranes prepared from rats repeatedly treated with pargyline (at doses which block MAO tipo A and B) but not with minaprine, the number of 5HT1C and 5HT2 receptors was reduced. 6. Repeated administrations of minaprine but not of pargyline increased the Bmax values of [3H]-imipramine binding. In 5, 7-DHT lesioned rats minaprine failed to increase the number of the residual [3H]-imipramine recognition sites. 7. The authors conclude that the increase in the number of [3H]-imipramine recognition sites is unrelated to the IMAO activity of minaprine. 8. The presence of 5HT axons on which [3H]-imipramine recognition sites are located is an absolute requirement for the clinical efficacy of minaprine. 9. The action of minaprine in the regulation of the synthesis and/or of the release of an endogenous substance that is important in mediating brain beta-adrenergic function is discussed.
Biochemical effects of minaprine on striatal dopaminergic neurons in rats
The biochemical effects of minaprine, a new psychotropic drug, were investigated on striatal dopaminergic neurons in the rat. Minaprine did not displace [3H]spiperone in-vitro binding from striatal membranes but had clear effects on dopamine (DA) metabolites. Homovanillic acid (HVA) and dihydroxyphenylacetic acid (DOPAC) were significantly decreased in a dose-dependent manner after intraperitoneal administration of minaprine 30 min before killing. In rats injected with minaprine 15 mg kg-1 i.p. at different intervals, the decrease in striatal HVA and DOPAC was time-dependent and a concomitant rise in 3-methoxytyramine (3-MT) concentrations was observed. The maximum of these effects was reached 30 min after minaprine. When administered 5 min after a monoamineoxidase (MAO) inhibitor (pargyline, 100 mg kg-1 i.p.) and 30 min before killing, minaprine did not affect pargyline-induced changes in HVA, DOPAC and 3-MT levels. This together with other data suggests that minaprine affects DA metabolism by acting, at least partially, at presynaptic level through in-vivo inhibition of MAO activity.