|Name||Deschloroclozapine dihydrochloride (DCZ) (water soluble)|
|Description||Potent, selective and metabolically stable hM3Dq and hM4Di muscarinic DREADD actuator. Water soluble.|
|Biological description|| |
Deschloroclozapine (DCZ) is reported to be a potent, selective and highly brain-penetrable muscarinic hM3Dq and hM4Di DREADD actuator with minimal off-target actions (Ki = 6.3 and 4.2 nM at hM3Dq and hM4Di respectively) and (EC50 values are 0.13 and 0.081 nM at hM3Dq and hM4Di respectively in a BRET-based assay.
It represents a potent, selective, metabolically stable and fast acting DREADD agonist with utility in both mice and non-human primates for a variety of applications.
It shows 100-fold improved affinity and greater agonist potency for hM3Dq and hM4Di compared to Clozapine n-Oxide (CNO) or DREADD agonist 21 (C21) with reduced off-target binding compared with clozapine in vitro.It has lower affinity at D1, D2 and 5-HT2A and 5-HT2C receptors compared with clozapine.
PET studies demonstrate the compound is rapidly brain penetrable, is apparently selective and doses for DREADD occupancy are 20-fold and 60-fold lower than CNO or DREADD agonist 21 (C21) respectively.
Uses and applications
Systemic delivery of low doses of DCZ (1 or 3 µg/kg) were shown to enhance neuronal activity via hM3Dq in mice and monkeys within minutes.
Intramuscular doses of 100 µg/kg reversibly induced spatial working memory deficits in hM4Di expressing monkeys.
Deschloroclozapine freebase also available.
Solubility & Handling
|Solubility overview||Soluble in water (100 mM). Always store solutions at -20°C.|
Storage of solid
Storage of solutions
Storage of solutions at room temperature
|Important||This product is for RESEARCH USE ONLY and is not intended for therapeutic or diagnostic use. Not for human or veterinary use|
|Chemical name||6-(4-methylpiperazin-1-yl)-11H-benzo[b][1,4]benzodiazepine dihydrochloride|
|CAS Number||1977-07-7 (free base)|
References for Deschloroclozapine dihydrochloride (DCZ) (water soluble)
Deschloroclozapine, a potent and selective chemogenetic actuator enables rapid neuronal and behavioral modulations in mice and monkeysNagai et al (2020) Nature Neuroscience : 1157-1167
Chemogenetic actuator drugs impair prefrontal cortex-dependent working memory in rhesus monkeysUpright and Baxter (2019) bioRxiv : https://doi.org/10.1101/864140
Binding of 5H-dibenzo[b,e][1,4]diazepine and chiral 5H-dibenzo[a,d]cycloheptene analogues of clozapine to dopamine and serotonin receptors.Phillips et al (1994) J Med Chem 37(17) : 2686-96
Oestrogen engages brain MC4R signalling to drive physical activity in female miceKrause et al (2021) Nature. 599 : 131-135PubMedID: 34646010
Estrogen Drives Melanocortin Neurons To Increase Spontaneous Activity and Reduce Sedentary BehaviorKrause et al (2021) bioRxiv doi: : https://doi.org/10.1101/794792
Behavioral and slice electrophysiological assessment of DREADD ligand, deschloroclozapine (DCZ) in ratsNentwig et al (2021) bioRxiv https://doi.org/10.1101/2021.10.25.465454 : .