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First-pass extracted concept

clozapine

Candidate: concept label2 source documents4 linked claims
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Aliases

CLZ, low-dose clozapine

Extracted Explainers

What the tool is doing

Clozapine is used here as one of the chemogenetic actuators supporting the suppression experiment.

Source 1DOIPubMed

Clozapine is used here as a chemogenetic actuator ligand intended to trigger DREADD-induced manipulations after systemic administration.

Source 2DOIPubMed

Resources required

Its use requires a compatible chemogenetic setup, though the abstract does not specify the construct or dosing details.

Source 1DOIPubMed

What problem it solves

It helps cross-validate whether the reported network and behavioral findings are reproducible across actuator conditions.

Source 1DOIPubMed

It supplies the ligand needed to activate DREADDs in vivo.

Source 2DOIPubMed

What it does not solve

The abstract does not resolve pharmacological interpretation or off-target concerns.

Source 1DOIPubMed

The abstract indicates it is not inert in naïve NHPs and can confound interpretation through off-target effects.

Source 2DOIPubMed

Alternatives

The abstract explicitly names clozapine-N-oxide as the alternative actuator used for cross-validation.

Source 1DOIPubMed

The paper contrasts clozapine with deschloroclozapine, and the results favor low-dose DCZ for future DREADD-based experiments.

Source 2DOIPubMed

Evidence Snippets

Our results were cross-validated using two different chemogenetic actuators, clozapine (CLZ) and clozapine-N-oxide (CNO).
Evidence 1Source 1DOIPubMedprovenance
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.
Evidence 2Source 2DOIPubMedprovenance

Supporting Sources

Linked Claims

Claim 1cross validationsupports2024Source 1DOIPubMed

The reported results were cross-validated using clozapine and clozapine-N-oxide as two chemogenetic actuators.

Quoted textsource-backed
Our results were cross-validated using two different chemogenetic actuators, clozapine (CLZ) and clozapine-N-oxide (CNO).
Claim 2off target effectsupports2023Source 2DOIPubMed

Clozapine administration induced consistent changes in rs-FC and INTs prior to DREADD expression in the study subjects.

Quoted textsource-backed
In contrast, CLZ administration induced consistent changes in rs-FC and INTs prior to DREADD expression in our subjects.
Claim 3recommendationsupports2023Source 2DOIPubMed

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 4selectivity and off targetsupports2023Source 2DOIPubMed

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.