A growing number of ligands that can be used to activate RASSLs / DREADDs are commercially available.
CNO is the prototypical DREADD activator. CNO activates the excitatory Gq- coupled DREADDs: hM3Dq, hM1Dq and hM5Dq and also the inhibitory hM4Di and hM2Di G-coupled DREADDs. CNO also activates the G-coupled DREADD (GsD) and the β-arrestin preferring DREADD: rM3Darr (Rq(R165L). 
Recent findings suggest that systemically administered CNO does not readily cross the blood-brain-barrier in vivo and converts to clozapine which itself activates DREADDs. Clozapine is an atypical antipsychotic which has been indicated to show high DREADD affinity and potency. Subthreshold injections of clozapine itself can be utilised to induce preferential DREADD-mediated behaviors. Therefore, when using CNO, care must be taken in experimental design and proper controls should be incorporated. 
DREADD agonist 21, also known as Compound 21, represents an alternative agonist for muscarinic-based DREADDs and an alternative to CNO. It has been reported that Compound 21 has excellent bioavailability, pharmacokinetic properties and brain penetrability and does not undergo reverse metabolism to clozapine. Another known agonist is perlapine, a hypnotic drug approved for treating insomnia in Japan. It acts as an activator of G-, G-, and G DREADDs that has structural similarity to CNO. A more recent agonist of hM3Dq and hM4Di is deschloroclozapine (DCZ). 
On the other hand, SalB B is a potent and selective activator of KORD. 
JHU37160 and JHU37152 have been marketed commercially as novel DREADD ligands, active in vivo, with high potency and affinity for hM3Dq and hM4Di DREADDs.
Diihydrochloride salts of DREADDs ligands that are water-soluble (but with differing stabilities in solution) have also been commercially developed (see  for aqueous stability).