Deschloroclozapine

• CAT Number: I013043
• CAS Number: 1977-07-7
• Molecular Formula: C18H20N4
• Molecular Weight: 292.38
• Purity: ≥95%

Deschloroclozapine, a metabolite of Clozapine, is a highly potent muscarinic DREADDs agonist. Deschloroclozapine binds to DREADD receptor subtypes hM3Dq and hM4Di with Ki of 6.3 and 4.2 nM, respectively. [11C]-Deschloroclozapine is developed as a promising PET tracer for DREADD imaging[1][2][3].
Designer Receptors Exclusively Activated by Designer Drugs (DREADD) are a chemogenetic approach for remote manipulation of neuronal activity in freely-moving animals. DREADDs comprise mutated G protein-coupled receptors (GPCRs) that do not respond to their endogenous neurotransmitter, but do respond to an otherwise “inert” exogenous substance[2].
Deschloroclozapine (0.3 mg/kg; intramuscularly) impairs working memory function in male rhesus macaques (aged between 5 and 6 years and weighing 5.5-7.9 kg)[3].
Deschloroclozapine (0.1 mg/kg; i.m) is effective at activating DREADD receptors in vivo and reversibly inducing behavioral effects in monkeys[3].

Reference

[1]. Maggs JL, et al. The metabolic formation of reactive intermediates from clozapine, a drug associated with agranulocytosis in man. J Pharmacol Exp Ther. 1995;275(3):1463-1475.
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[2]. Hu F, et al. 18F-labeled radiotracers for in vivo imaging of DREADD with positron emission tomography. Eur J Med Chem. 2021;213:113047.
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[3]. Upright NA, et al. Effect of chemogenetic actuator drugs on prefrontal cortex-dependent working memory in nonhuman primates. Neuropsychopharmacology. 2020;45(11):1793-1798.
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