N-Desmethylclozapine

6104-71-8

C17H17ClN4

DMSO : >= 50 mg/mL (159.85 mM)

GPCR/G Protein; Neuronal Signaling; Metabolic Enzyme/Protease

N-Desmethylclozapine is a dengue virus inhibitor, and an agonist of delta-opioid receptor. In Vitro: The IC₅₀s of N-desmethylclozapine, fluoxetine hydrochloride, and salmeterol xinafoate in Huh-7 cells infected with DENV-2 are 1 uM, 0.38 uM, and 0.67 uM, respectively. The levels of NS3 are reduced in cells treated with all three inhibitors compared to DMSO treatment, suggesting that the inhibitors act at a stage prior to viral protein translation. N-Desmethylclozapine-treated cells show a >75% reduction in negative-strand RNA levels^[1]. N-desmethylclozapine exhibits slight agonistic effects on the M1 mAChR, and agonistic properties at the 5-HT1A receptor in the cerebral cortex and hippocampus. This compound also behaves as an agonist at the delta-opioid receptor in the cerebral cortex and striatum^[2]. N-desmethylclozapine (3 uM) greatly decreases the outward current in excitatory neurons, but not in inhibitory neurons. In excitatory neurons, N-desmethylclozapine alone is more effective than either clozapine alone or the combination of clozapine and N-desmethylclozapine. The effect of N-desmethylclozapine in excitatory neurons is significantly suppressed by 0.1 uM pirenzepine and 1 uM atropine. N-desmethylclozapine, but not clozapine, suppressed K⁺ channels via M1 receptors in excitatory cells^[3]. N-desmethylclozapine leads to a decrease in TxB2 levels under unstimulated conditions as well as under TSST-1 stimulation. Clozapine, N-desmethylclozapine and CPZ possibly act on neurotransmitter systems via modulation of TxA2 or TxB2 production^[5]. In Vivo: N-desmethylclozapine in rat and human at M2 and M4 mAChRs underlying presynaptic modulation of GABA and glutamate release, respectively. In particular, N-desmethylclozapine maybe a M2 mAChR antagonist in the rat but has no activity at this receptor in human neocortex. However, N-desmethylclozapine has an agonistic effect at M4 mAChR in the human but no such effect in the rat neocortex^[4].