Adrenoceptors are ubiquitous and regulate most vital functions in the human body, including heart and respiratory rate, digestion, smooth-muscle contraction, gland secretion, and pupil diameter among others. In addition, adrenergic neurons firing from the locus coeruleus towards different areas of the central nervous system mediate alertness, responses to acute stress and danger, pain modulation, arousal, sleepwake cycles, as well as neuroplasticity and cognitive behaviour. Despite the physiological relevance of adrenergic neurotransmission, molecular methods to precisely modulate the activity of endogenous adrenoceptor and to functionally dissect their pathways in vivo are not available. Here we present a set of photochromic ligands, that we call adrenoswitches, to switch on and off adrenoceptor activity with high spatio-temporal resolution. Using a non-canonical azologization approach, we have designed novel arylazoheteroarene units that we have characterized in vitro and in two animal models (zebrafish locomotion and pupillary reflex in mice). The drug-like properties of these molecules, their efficacy and absence of acute toxicity in zebrafish larvae, and most remarkably the fact that specific adrenergic photomodulation was readily and reversibly achieved in the mammalian eye by topical application without formulation, all indicate that adrenoswitches could be a disruptive tool to dissect physiological adrenergic signalling and to develop safe and effective therapies. For example, photocontrol of adrenoceptors at specific locations might allow to single out individual adrenergic projections from the locus coeruleus, or to selectively decouple pupil tone from environmental illumination.