A promising therapeutic potential has been reported in a number of clinical studies for botulinum neurotoxin (BOTOX) which reversibly inhibits release of neurotransmitters at synapses, especially at neuromuscular junctions. Importantly, this neurotoxin does not compromise neuronal well-being and neurotransmission resumes after four months. Recently, botulinum neurotoxin has been approved for treatment of migraine; however, the fear of muscle paralysis restricts the use of native neurotoxin for pain management and other hypersecretory conditions. We recently developed new botulinum molecules which have a more selective action. Specifically, our molecules target CNS neurons but do not cause muscle paralysis. This feature makes our molecules attractive for treatment of chronic secretory disorders with a promise of targeted neuronal silencing.