|Name||DREADD agonist 21 (Compound 21) dihydrochloride (water soluble)|
|Description||Effective agonist for muscarinic-based DREADDs in vitro and in vivo. Non-CNO chemogenetic actuator. Brain penetrant. Water soluble.|
|Customer comments|| |
We used Compound 21 (DREADD agonist 21) dihydrochloride (water soluble) (1mg/kg) and CNO in rats (1mg/kg) and we found a great effect on cells infected with dreadds-Gs. Both products are really easy to dissolve in saline! Verified customer, Universite de Bordeaux
Great Product!, Product was delivered promptly. Very easy to work with. No problems keeping it in solution. Verified customer, Florida Atlantic University
|Biological description|| |
DREADD agonist 21 (Compound 21) hydrochloride is a water soluble salt of DREADD agonist 21 (Compound 21) which represents an alternative chemogenetic actuator for muscarinic -based DREADDs and an alternative to CNO for in vivo studies in which metabolic conversion of CNO to clozapine is an issue.
DREADD agonist 21 from Hello Bio has recently been cited in a pharmacokinetic profile of the compound in mice by Jendryka et al (2019) which suggests that DREADD agonist 21 shows superior brain penetration and long-lasting presence. They suggest that the compound is a suitable DREADD agonist (0.4-1 mg/kg) which is effective at latest 15 min after i.p injection, but requires between-subject controls for unspecific effects.
Figure: In vivo pharmacokinetic profile of DREADD agonist 21 (Cmpd-21). DREADD agonist 21 was from Hello Bio.
(j–l): Concentration (nM) of Cmpd-21 (blue) at 15, 30 and 60 min after i.p. injection of 3.0 mg/kg Cmpd-21 in (j) plasma, (k) CSF, and (l) cortical brain tissue. Reproduced from Jendryka et al Sci Rep. 2019;9(1):4522
Bonavenutra (2018) suggest that the compound exhibits lower in vivo DREADD potency than clozapine and is not efficient in nonhuman primate (NH) applications.
Bonavenutra (2018) reported DREADD ligands while efficacious in certain applications may not display sufficient potency or selectivity in others.
Care should therefore be taken with in vivo dosing of DREADD agonist 21 to ensure the free concentration of the compound remains in a range that activates muscarinic DREADDs but is sufficiently low to avoid antagonism at wild type GPCRs.
Solubility & Handling
|Storage instructions||-20°C (desiccate)|
|Solubility overview||Soluble in water (100mM). Always store solutions at -20°C.|
Storage of solid
Storage of solutions
|Handling continued..|| |
|Important||This product is for RESEARCH USE ONLY and is not intended for therapeutic or diagnostic use. Not for human or veterinary use|
|Chemical name||11-(1-Piperazinyl)-5H-dibenzo[b,e][1,4]diazepine dihydrochloride|
References for DREADD agonist 21 (Compound 21) dihydrochloride (water soluble)
Compound 21, a two-edged sword with both DREADD-selective and off-target outcomes in ratsGoutaudier et al (2020) PLOS ONE 15(9): : e0238156
Pharmacokinetic and pharmacodynamic actions of clozapine-N-oxide, clozapine, and compound 21 in DREADD-based chemogenetics in mice.Jendryka et al (2019) Sci Rep. 9(1) : 4522
High-potency ligands for DREADD imaging and activation in rodents and monkeysBonaventura et al (2019) Nat Commun . 4627 : 10(1)PubMedID: https://pubmed.ncbi.nlm.nih.gov/
DREADDs: The Power of the Lock, the Weakness of the Key. Favoring the Pursuit of Specific Conditions Rather than Specific Ligands.Goutaudier et al (2019) eNeuro 6 : (5)
DREADD Agonist 21 Is an Effective Agonist for Muscarinic-Based DREADDs in Vitro and in VivoThompson et al (2018) ACS Pharmacol. Transl. Sci. 10.1021 : /acsptsci.8b00012
Improvement of sensory deficits in Fragile X mice by increasing cortical interneuron activity after the critical periodPortera-Cailliau et al (2022) Biorxiv : https://doi.org/10.1101/2022.05.17.492368
Chemogenetic dissection of prefrontal signalling underlying attention and impulsivityvan der Veen et al (2022) Universität Ulm : Thesis
Chemogenetic activation of midline thalamic nuclei fails to ameliorate memory deficits in two mouse models of Alzheimer's diseaseT Craig et al (2022) bioRxiv https://doi.org/10.1101/2021.06.30.450500 : doi
Microglia modulate blood flow, neurovascular coupling, and hypoperfusion via purinergic actionsCsaszar et al (2022) J Exp Med 219 : 3PubMedID: 35201268
Activation of the Lateral Habenula-Ventral Tegmental Area Neural Circuit Contributes to Postoperative Cognitive Dysfunction in MiceXin J et al (2022) Adv Sci (Weinh) 9(22) : e2202228PubMedID: 35616407