First-pass extracted concept

deschloroclozapine

Candidate: concept label3 source documents9 linked claims

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Aliases

DCZ, low-dose DCZ

Extracted Explainers

What the tool is doing

Deschloroclozapine is used as a chemogenetic actuator ligand for DREADD experiments after systemic administration.

Source 3DOI PubMed

What problem it solves

It provides a DREADD actuator option that the authors found less confounding than clozapine at low dose in naïve NHP imaging.

Source 3DOI PubMed

What it does not solve

The abstract does not support that DCZ is universally inert, because high dose caused subject-specific rs-FC and INT changes.

Source 3DOI PubMed

Alternatives

The paper directly compares DCZ with clozapine and concludes that low-dose DCZ is preferable for future DREADD-based experiments.

Source 3DOI PubMed

Evidence Snippets

Subcutaneous deschloroclozapine in rats transfected with AAV9 resulted in a substantial reduction of food-intake, comparable to the efficacy of exenatide. We estimated that the effect of deschloroclozapine lasts 1-3 h post-administration.

Evidence 1Source 1DOI PubMedprovenance

This study investigates the in vivo electrophysiological effects of DREADD actuation by deschloroclozapine.

Evidence 2Source 2DOI PubMedprovenance

Actuator ligands low-dose clozapine (CLZ) and deschloroclozapine (DCZ) are highly selective for DREADDs... Low-dose DCZ did not induce consistent changes in rs-FC or INTs prior to the expression of DREADDs; however, a high dose resulted in subject-specific changes in rs-FC and INTs.

Evidence 3Source 3DOI PubMedprovenance

Supporting Sources

Source 1primary paper2024MEDDOI PubMed

1 evidence snippet 3 linked claims Claim 1 Claim 2 Claim 3

Source 2primary paper2024MEDDOI PubMed

1 evidence snippet 2 linked claims Claim 1 Claim 2

Source 3primary paper2023MEDDOI PubMed

1 evidence snippet 4 linked claims Claim 1 Claim 2 Claim 3

Linked Claims

Claim 1comparative efficacysupports2024Source 1DOI PubMed

AAV5, oral deschloroclozapine, and clozapine-N-oxide were effective but slightly less potent than the strongest reported condition.

Quoted textsource-backed

AAV5, oral administration of deschloroclozapine, and clozapine-N-oxide were also effective but with slightly less potency.

Claim 2comparative efficacysupports2024Source 1DOI PubMed

Subcutaneous deschloroclozapine in AAV9-transfected rats produced a substantial reduction in food intake comparable to exenatide.

Quoted textsource-backed

Subcutaneous deschloroclozapine in rats transfected with AAV9 resulted in a substantial reduction of food-intake, comparable to the efficacy of exenatide.

Claim 3durationsupports2024Source 1DOI PubMed

The effect of deschloroclozapine was estimated to last 1-3 hours after administration.

Quoted textsource-backed

We estimated that the effect of deschloroclozapine lasts 1-3 h post-administration.

Claim 4electrophysiology effectsupports2024Source 2DOI PubMed

Deschloroclozapine actuation of pan-neuronal hM3D(Gq) in rat anterior cingulate cortex produced inhibitory effects in a significant portion of neurons in vivo.

Quoted textsource-backed

Unexpectedly, in response to the administration of deschloroclozapine, we observed inhibitory effects with pan-neuronal hM3D(Gq) stimulation

Claim 5electrophysiology effectsupports2024Source 2DOI PubMed

Deschloroclozapine actuation of pan-neuronal hM4D(Gi) in rat anterior cingulate cortex produced excitatory effects in a significant portion of neurons in vivo.

Quoted textsource-backed

and excitatory effects with pan-neuronal hM4D(Gi) stimulation in a significant portion of neurons

Claim 6dose dependencesupports2023Source 3DOI PubMed

High-dose DCZ produced subject-specific changes in rs-FC and INTs in naïve nonhuman primates prior to DREADD expression.

Quoted textsource-backed

however, a high dose resulted in subject-specific changes in rs-FC and INTs

Claim 7off target effectsupports2023Source 3DOI PubMed

Low-dose DCZ did not induce consistent changes in rs-FC or INTs prior to DREADD expression in naïve nonhuman primates.

Quoted textsource-backed

Low-dose DCZ did not induce consistent changes in rs-FC or INTs prior to the expression of DREADDs

Claim 8recommendationsupports2023Source 3DOI PubMed

The results caution against using clozapine because off-target effects can confound experimental results and endorse low-dose DCZ for future DREADD-based experiments.

Quoted textsource-backed

Our results caution against the use of CLZ by explicitly demonstrating the impact of off-target effects that can confound experimental results. Altogether, these data endorse the use of low dose DCZ for future DREADD-based experiments.

Claim 9selectivity and off targetsupports2023Source 3DOI PubMed

Clozapine and deschloroclozapine are reported as highly selective for DREADDs but both also have partial affinity for endogenous receptors and can cause dose-specific changes in naïve animals.

Quoted textsource-backed

Actuator ligands low-dose clozapine (CLZ) and deschloroclozapine (DCZ) are highly selective for DREADDs... Despite this reported specificity, both CLZ and DCZ have partial affinity for a variety of endogenous receptors and can induce dose-specific changes even in naïve animals.