洛沙平是一种口服活性多巴胺抑制剂、5-HT 受体拮抗剂，也是一种二苯并沙西平抗精神病药物。
Loxapine Succinate is a D2DR and D4DR inhibitor, serotonergic receptor antagonist and also a dibenzoxazepine anti-psychotic agent [1].
In vitro: Loxapine was a typical neuroleptic that showed great structural and functional homology to the atypical antipsychotic clozapine. Chronic loxapine treatment was usually associated with extrapyramidal symptoms (EPS). Loxapineexihibited an extremely strong binding affinity fordopamineD4 andserotonin5-HT2receptors, suggesting that both serotonergic and dopaminergic mechanisms contributed to the antipsychotic drug action and EPS associated with loxapine in the treatment of schizophrenia [1]. In frontal cortex of brain in human and bovine, in the presence of Loxapine, [3H]ketanserin bound to 5-HT2 receptor with ki value of 6.2 nM and 6.6 nM, respectively. In comparing competition experiments involving the human membranes, loxapine exihibited the rank order of potency for the various receptors as follows: 5-HT2≥D4>>>D1>D2 [1]. Loxapine administration at 0.2, 2 and 20 μMafter 1 and 3 days of exposure reduced IL-1βand IL-2 secretion by LPS-activated mixed glia cultures. Loxapine also decreased IL-1βand IL-2 secretion in LPS-induced microglia cultures [2].
In vivo: Chronic administration of loxapine(5 mg/kg) in rats for 4 weeks or 10 weeks significantly reduced more than 50% of serotonin (S2) receptor density. Loxapine (5 mg/kg) didn’t change dopamine receptor density but greatly reduced serotonin receptor density by 47% in the brain of rats [3].
参考文献:
[1].? Singh AN1,Barlas C,Singh S,Franks P,Mishra RK. A neurochemical basis for the antipsychotic activity of loxapine: interactions withdopamineD1,D2, D4 andserotonin5-HT2receptorsubtypes.J Psychiatry Neurosci.1996 Jan;21(1):29-35.
[2].? Labuzek K1,Kowalski J,Gabryel B,Herman ZS. Chlorpromazine and loxapine reduce interleukin-1beta and interleukin-2 release by rat mixed glial and microglial cell cultures.Eur Neuropsychopharmacol.2005 Jan;15(1):23-30.
[3].? Lee T,Tang SW. Loxapine and clozapine decreaseserotonin(S2) but do not elevatedopamine(D2)receptornumbers in the rat brain.Psychiatry Res.1984 Aug;12(4):277-85.
| Cell experiment [1]: | |
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Cell lines |
Rat glial and microglial cells |
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Preparation method |
This compound is soluble in DMSO. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 °C for several months. |
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Reacting condition |
0.2, 2 and 20 μM; 1 and 3 days |
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Applications |
In LPS-activated rat mixed glial and microglial cell cultures, Loxapine at all indicated concentrations reduced IL-1β secretion. Besides, Loxapine also reduced IL-2 secretion in mixed glia cultures. In addition, in LPS-induced microglia cultures, Loxapine decreased both IL-1β and IL-2 secretion at the concentrations of 0.2, 2 and 20 μM after the exposure of 1 and 3 days. |
| Animal experiment [2]: | |
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Animal models |
Wistar rats |
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Dosage form |
5 mg/kg; i.p. |
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Applications |
In Wistar rats, chronic administration of Loxapine for 4 weeks or 10 weeks did not increase striatal dopamine receptor density. However, Loxapine significantly reduced cortical serotonin receptor density by 50 ~ 60%. In addition, a single dose of Loxapine exhibited the same potent effect. The results suggested that Loxapine exerted its effect via the serotonin system. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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参考文献: [1]. Labuzek K1,Kowalski J,Gabryel B,Herman ZS. Chlorpromazine and loxapine reduce interleukin-1beta and interleukin-2 release by rat mixed glial and microglial cell cultures.Eur Neuropsychopharmacol.2005 Jan;15(1):23-30. [2]. Lee T,Tang SW. Loxapine and clozapine decreaseserotonin(S2) but do not elevatedopamine(D2)receptornumbers in the rat brain.Psychiatry Res.1984 Aug;12(4):277-85. | |
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