Deschloroclozapine dihydrochloride是一种高亲和力、选择性且代谢稳定的毒蕈碱DREADD激动剂，Deschloroclozapine dihydrochloride能快速穿透血脑屏障，有效激活兴奋性hM3Dq和抑制性hM4Di DREADD受体。
Sample solution is provided at 25 µL, 10mM.
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Deschloroclozapine dihydrochloride is a high-affinity, selective, and metabolically stable muscarinic DREADD agonist. Deschloroclozapine dihydrochloride can rapidly cross the blood-brain barrier and effectively activate both excitatory hM3Dq and inhibitory hM4Di DREADD receptors[1-2]. Deschloroclozapine dihydrochloride is primarily used in neuroscience for chemogenetic research to precisely modulate neuronal activity[3-4].
In vivo, In transgenic neuropathic pain model rats expressing hM3Dq, subcutaneous injection of Deschloroclozapine dihydrochloride (0.1mg/kg) for 120 minutes significantly increased serum OXT levels and rapidly raised the rats' mechanical pain threshold[5]. In transgenic mice expressing hM3Dq, intraperitoneal administration of Deschloroclozapine dihydrochloride (1mg/kg) for 5–10 minutes rapidly enhanced neuronal activity via hM3Dq, with an efficacy more than 2.5 times greater than that of Clozapine N-oxide (CNO; 100μg/kg), and brain concentrations of Deschloroclozapine dihydrochloride reached approximately 100 nM at 30 minutes[6].
References:
[1] Maggs JL, Williams D, Pirmohamed M, et al. The metabolic formation of reactive intermediates from clozapine, a drug associated with agranulocytosis in man. J Pharmacol Exp Ther. 1995 Dec;275(3):1463-75.
[2] Zhang S, Gumpper RH, Huang XP, et al. Molecular basis for selective activation of DREADD-based chemogenetics. Nature. 2022 Dec;612(7939):354-362.
[3] Nentwig TB, Obray JD, Vaughan DT, et al. Behavioral and slice electrophysiological assessment of DREADD ligand, Deschloroclozapine dihydrochloride (DCZ) in rats. Sci Rep. 2022 Apr 21;12(1):6595.
[4] Hu F, Morris PJ, Bonaventura J, et al. 18F-labeled radiotracers for in vivo imaging of DREADD with positron emission tomography. Eur J Med Chem. 2021 Mar 5;213:113047.
[5] Nagai Y, Miyakawa N, Takuwa H, et al. Deschloroclozapine dihydrochloride, a potent and selective chemogenetic actuator enables rapid neuronal and behavioral modulations in mice and monkeys. Nat Neurosci. 2020 Sep;23(9):1157-1167.
[6] Shimizu M, Yoshimura M, Baba K, et al. Deschloroclozapine dihydrochloride exhibits an exquisite agonistic effect at lower concentration compared to clozapine-N-oxide in hM3Dq expressing chemogenetically modified rats. Front Neurosci. 2023 Nov 30;17:1301515.
Deschloroclozapine dihydrochloride是一种高亲和力、选择性且代谢稳定的毒蕈碱DREADD激动剂，Deschloroclozapine dihydrochloride能快速穿透血脑屏障，有效激活兴奋性hM3Dq和抑制性hM4Di DREADD受体[1-2]。Deschloroclozapine dihydrochloride主要用于神经科学领域的化学遗传学研究，以精确调控神经元活动[3-4]。
在体内，对表达hM3Dq的转基因的神经病理性疼痛模型大鼠，皮下注射Deschloroclozapine dihydrochloride（0.1mg/kg）处理120分钟，Deschloroclozapine dihydrochloride显著升高血清OXT浓度，且快速提大鼠的机械痛阈[5]。对表达hM3Dq的转基因小鼠腹腔注射Deschloroclozapine dihydrochloride（1mg/kg）处理5-10分钟，Deschloroclozapine dihydrochloride通过hM3Dq快速增强神经元活性，效果强度为Clozapine N-oxide（CNO；100μg/kg）的2.5倍以上，且脑内Deschloroclozapine dihydrochloride浓度在30分钟时达100nM[6]。
| Animal experiment [1]: | |
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Animal models |
OXT-hM3Dq-mCherry transgenic rats (adult male). |
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Preparation Method |
Rats were subcutaneously (s.c.) administered a single dose of Deschloroclozapine dihydrochloride (0.1mg/kg). Serum oxytocin (OXT) concentrations were measured at 0, 10, 30, 60, 120, and 180 minutes post-injection. Brain neuronal activity (Fos expression) was assessed 120 minutes post-injection. In a neuropathic pain model (Seltzer model), behavioral tests (von Frey test, Rat Grimace Scale, hot plate test) were conducted at 0, 10, 30, 60, 120, and 180 minutes post-Deschloroclozapine dihydrochloride administration. |
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Dosage form |
0.1mg/kg; s.c.; Single injection. |
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Applications |
Deschloroclozapine dihydrochloride administration induced a rapid and robust increase in serum OXT levels, Deschloroclozapine dihydrochloride significantly enhanced neuronal activation (Fos expression) in brain regions including the SON, PVN, and PAG comparable to a 10-fold higher dose of CNO, and produced rapid analgesic effects in a neuropathic pain model (significantly increasing mechanical nociceptive threshold and reducing pain scores within 10 minutes). |
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References: |
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| Cas No. | SDF | ||
| 分子式 | C18H22Cl2N4 | 分子量 | 365.3 |
| 溶解度 | H2O : 100 mg/mL (273.75 mM; Need ultrasonic); DMSO : 80 mg/mL (219.00 mM; ultrasonic and adjust pH to 7 with 1 M NaOH) | 储存条件 | -20°C, sealed storage, away from moisture |
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.7375 mL | 13.6874 mL | 27.3748 mL |
| 5 mM | 547.5 μL | 2.7375 mL | 5.475 mL |
| 10 mM | 273.7 μL | 1.3687 mL | 2.7375 mL |
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