ADORA2A and attention deficit-hyperactivity disorder: For example, the nonselective α2A/2CR agonists clonidineand guanfacine (Figure 1) are approved to treat attention-deficit-hyperactivity disorder(ADHD)8,15,16 and the nonselectiveα2AR/α2CR agonist lofexidine is approved to treat opioidwithdrawal symptoms.17−19 All three approved α2R agonists cause sedation.19−22 In addition, data from transgenic mice models suggest the cognitive14,23 and neurochemical24,25 benefits of these drugs may comefrom α2AR activation alone and α2CR activation may bedeleterious to the benefits obtained from α2AR activation.