There will be a HazMat fee per item when shipping a dangerous goods. The HazMat fee will be charged to your UPS/DHL/FedEx collect account or added to the invoice unless the package is shipped via Ground service. Ship by air in Excepted Quantity (each bottle), which is up to 1g/1mL for class 6.1 packing group I or II, and up to 25g/25ml for all other HazMat items.
Type
HazMat fee for 500 gram (Estimated)
Excepted Quantity
USD 0.00
Limited Quantity
USD 15-60
Inaccessible (Haz class 6.1), Domestic
USD 80+
Inaccessible (Haz class 6.1), International
USD 150+
Accessible (Haz class 3, 4, 5 or 8), Domestic
USD 100+
Accessible (Haz class 3, 4, 5 or 8), International
Clozapine N-oxide, a primary metabolite of Clozapine, serves as an agonist for human muscarinic designer receptors (DREADDs), effectively activating DREADD receptors hM3Dq and hM4Di, and is capable of crossing the blood-brain barrier[1].[2].[3].[4]. Clozapine itself is known as a powerful antagonist of dopamine and a selective agonist for the muscarinic M4 receptor, with an EC50 value of 11 nM[5].[6].
体内研究
After a single intraperitoneal injection of 1 mg/kg Clozapine N-oxide into mice, peak plasma levels of CNO are reached at 15 minutes, declining significantly after 2 hours. Despite this short plasma half-life in mice, the physiological and behavioral effects described following acute treatment in DREADD-expressing experimental animals typically extend much longer, between 6-10 hours[1].
体外研究
Clozapine N-oxide (CNO) can bind to non-DREADD receptors at concentrations necessary for DREADD activation and can undergo reverse metabolism back to its parent compound clozapine, an atypical antipsychotic with a wide range of pharmacological targets and effects[2].
Clozapine N-oxide/氯氮平N-氧化物 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
Shank2/C0//C0 mouse model
Subcutaneous injection
5 mg/kg
Once daily for 5 days
Selective enhancement of MPOA activity by DREADD technology re-established social bonding behavior in Shank2/C0//C0 mice, providing evidence that the identified circuit might be crucial for explaining how social deficits in ASD can arise.
EMBO J. 2021 Mar 1;40(5):e104267
Mice
Spinal cord injury model
10 mg/kg
Single administration, effects evaluated at 1 h and 24 h post-administration
To assess the impact of inhibiting neuronal activity of transplanted hM4Di-NS/PCs on locomotor function in mice, results showed that CNO administration significantly reduced locomotor function in the transplanted group.
Stem Cell Reports. 2022 Jan 11;17(1):127-142
Rats
Parkinson's disease rat model
Intraperitoneal injection
1 mg/kg
Single injection, lasting up to 10 hours
DREADD activation of PPN cholinergic neurons significantly reversed motor deficits and restored striatal dopamine signaling in Parkinsonian rats.
Neurotherapeutics. 2020 Jul;17(3):1120-1141
C57BL/6J mice
Binge-like ethanol drinking model
Intraperitoneal injection
1 mg/kg, 2 mg/kg
Administered 15-30 minutes prior to each DID session, lasting for 7 days
Activation of CeA to NAc core projection neurons reduced binge-like ethanol drinking, and this effect was dependent on CRF signaling.
Neuropharmacology. 2022 Feb 1;203:108874
Mice
Transgenic mice
Injection
5 μg/g
Single injection, 30 minutes before behavioral experiments
Activation of CEl CRH+ cells to increase passive behaviors
Mol Psychiatry. 2020 Feb;25(2):428-441
Mice
Gi-DREADD expressing mice
Intraperitoneal injection
5 mg/kg
Single administration
CNO targets Gi-DREDD to reduce endogenous NE release and subsequently increase microglial process surveillance.
Nat Neurosci. 2019 Nov;22(11):1771-1781
Mice
AgRP-Sirt1KO mice
Intraperitoneal injection
10 mg/kg
Once daily for 11-15 days
Clozapine prevented the loss of superficial layer PL mPFC neurons in AgRP-Sirt1KO mice and restored normal PPI response.
Mol Psychiatry. 2022 Oct;27(10):3951-3960
Mice
CRF-Cre mice
Intraperitoneal injection
3 mg/kg
Single administration
To investigate the effect of CNO on Gi-DREADD activation in CRF-Cre mice, results showed that CNO significantly suppressed binge alcohol drinking and reduced anxiety-like behavior.
Nat Neurosci. 2015 Apr;18(4):545-52.
Rats
TTX model
Intraperitoneal injection
1 mg/kg
Single dose
Activate DREADD receptors, increase spasm counts and clustering
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