A brain function is produced by the cooperative work of some brain areas responsible for the function. Since the breakdown of this mechanism induces the pathological conditions in neuropsychiatric disorders, it is important to identify the affected function by manipulating the specific brain regions. Designer receptors exclusively activated by designer drugs (DREADDs) are one of the chemogenetic technologies that afford a remotely reversible control of the activity of a target neural population expressing a "designer receptor" by an agonist compound. The most widely used DREADDs are muscarinic-based such as hM3Dq (excitatory) and hM4Di (inhibitory), which can be activated by clozapine-N-oxide (CNO). CNO has some concerns that the effect is slow because CNO has a modest brain penetrability, and the systemic administration may produce off-target actions because CNO is metabolized to clozapine, an antipsychotic drug that acts on numerous endogenous receptors. We solved these issues by developing a new compound, deschloroclozapine (DCZ). DCZ has a higher affinity and greater agonist potency than CNO with reduced off-target action and can rapidly modulate the neuronal activity and behavior with muscarinic-based DREADDs in living animals. Given the potential shortcomings of CNO, DCZ offers clear benefits to many users of muscarinic-based DREADD, with increased reliability by removing concerns about potential off-target responses.