DREADD agonist 21 (Compound 21) dihydrochloride (water soluble)(HB6124)
DREADD agonist 21 (Compound 21) dihydrochloride (water soluble)
Effective agonist for muscarinic-based DREADDs in vitro and in vivo. Non-CNO chemogenetic actuator. Brain penetrant. Water soluble.
DREADD agonist 21 (Compound 21) 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 (Compound 21) hydrochloride is a water soluble salt of DREADD agonist 21 which is a potent and selective agonist at muscarinic based DREADDs such as the excitatory hM3Dq, hM1Dq and inhibitory hM4Di DREADDs (pEC50 values are 8.48, 8.91 and 7.77 at hM3Dq, hM1Dq and hM4Di respectively).
DREADD agonist 21 (Compound 21) exhibits >10-fold higher affinity at hM1Dq and hM4Di DREADDs compared to wild type receptors and also lacks agonist activity at wild type receptors.
DREADD agonist 21 (Compound 21) has excellent bioavailability, pharmacokinetic properties and brain penetrability. It has been reported that DREADD agonist 21 does not undergo back metabolism to clozapine.
In vivo use
DREADD agonist 21 (Compound 21)-induced activation of hM3Dq and hM4Di can modulate bi-directional feeding in defined circuits in mice.
Concentrations of DREADD agonist 21 that resulted in changes in feeding behavior in animals expressing muscarinic DREADDs had no off-target effects in control animals (where musarinic DREADDs were not expressed).
DREADD agonist 21 shows weak to moderate binding affinity at a range of wild type GPCRs which may translate to functional antagonism in vivo.
Therefore care should 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.
In vivo experiments should be conducted with the appropriate controls where DREADD agonist 21 is administered to animals that do not express the muscarinic-DREADDs.
Data from a poster presented at SfN by the Michaelides group indicates that DREADD agonist 21 (Compound 21) has lower binding affinity for DREADDs compared to clozapine and that DREADD agonist 21 induces behavioural effects in transgenic mice. 1mg/kg doses were used. High doses (10mg/kg) may cause sedation.
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
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Storing and Using Your Product
Soluble in water (100mM). Always store solutions at -20°C.
Storage of solid
- Store at -20°C.
- Please note that the compound is a hydroscopic solid and contact with air may cause material to become sticky. Product performance should not be affected but we recommend storing the material in a sealed jar.
Storage of solutions
- Make up solutions and use immediately.
- If storage of solutions is required, you should aliquot out the solution into tightly sealed vials and store at -20°C and store these for up to one month.
- Allow the product to equilibrate to RT for at least one hour before opening and using.
Storage of solutions at room temperature
- We recommend only keeping solutions at room temperature (25°C) for a few days as our studies have shown that after 96 hours the purity of the compound in solution drops to ~95% and will continue to drop over time.
This product is for RESEARCH USE ONLY and is not intended for therapeutic or diagnostic use. Not for human or veterinary use
References for DREADD agonist 21 (Compound 21) dihydrochloride (water soluble)
The first structure-activity relationship studies for designer receptors exclusively activated by designer drugs.Chen et al (2015) ACS Chem Neurosci 6(3) : 476-84PubMedID: 25587888
Optogenetic approaches for dissecting neuromodulation and GPCR signaling in neural circuits.Spangler and Bruchas (2017) Curr Opin Pharmacol 32(4) : 56-70.PubMedID: 27875804
Clozapine N-Oxide Administration Produces Behavioral Effects in Long-Evans Rats: Implications for Designing DREADD Experiments.MacLaren et al (2016) eNeuro 3(5) : 0219-16PubMedID: 27822508
New non-CNO actuators for DREADDsRoth Bl (2015) Blog : N/A
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
Effects of Chemogenetic Inhibition of Dopamine Transporter-or A2A-Expressing Neurons On Spontaneous Activity and Motivation to Consume a Palatable FoodWherry(2018) Binghamton University : Thesis
Astrocytes Integrate Behavioral State and Vascular Signals during Functional HyperemiaTran et al (2018) Neuron doi: : https://doi.org/10.1016/j.neuron
Convergent inputs from the hippocampus and thalamus to the nucleus accumbens regulate dopamine neuron activityPerez and Lodge(2018) J Neurosci : 2629-16
Olanzapine: a full and potent agonist at the hM4D(Gi) DREADD amenable to clinical translation of chemogeneticsWeston et al (2018) bioRxiv doi: : https://doi.org/10.1101/477513
Microbiota imprint gut–intrinsic neuronal programming and sympathetic activityMuller and Mucida(2019) bioRxiv : doi: https://doi.org/10.1101/545
Reviews & Product Guides
Dissolves well, easy to use. Product easily dissolves in water, and injections seem to work as intended. Currently investigating whether oral consumption has similar effects in vivo.
Excellent product, easy to dissolve in saline. In vivo results suggest effective inhibition of hM4D-expressing neurons (and accompanying behavioral phenotype) with 1mg/kg i.p. administration.
Easy to use, seems effective. This compound dissolves easily in saline for in vivo use, and seems to have the desired effect in a similar dose range and time course as CNO. However, there did seem to be a slight locomotor effect after the first i.p. injection (1 mg/kg), which could not be replicated with further treatment.