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.
Soluble in water (100 mM). Always store solutions at -20°C.
Storage of solid
Store at -20°C.
Please note that the compound is a hydroscopic solid and contact with air may cause material to become sticky. Product performance should not be affected but we recommend storing the material in a sealed jar.
Storage of solutions
Make up solutions and use immediately.
If storage of solutions is required, you should aliquot out the solution into tightly sealed vials and store at -20°C and store these for up to one month.
Allow the product to equilibrate to RT for at least one hour before opening and using.
Storage of solutions at room temperature
We recommend only keeping solutions at room temperature (25°C) for a few days as our studies have shown that after 96 hours the purity of the compound in solution drops to ~97% and will continue to drop over time.
This product is for RESEARCH USE ONLY and is not intended for therapeutic or diagnostic use. Not for human or veterinary use