In line with its role as a first line defense system, SP is released when toxicants or poisons come into contact with a range of receptors on cellular elements in the chemoreceptor trigger zone , located in the floor of the fourth ventricle of the brain, the ( area postrema ). Presumably, SP is released in or around the nucleus of the solitary tract upon integrated activity of dopamine , serotonin , opioid , and/or acetylcholine receptor signaling. NK1Rs are stimulated. In turn, a fairly complex reflex is triggered involving cranial nerves sub-serving respiration, retroperistalsis, and general autonomic discharge. The actions of aprepitant are said to be entirely central, thus requiring passage of the drug into the central nervous system.  However, given that NK1Rs are unprotected by a blood brain barrier in the area postrema just adjacent to neuronal structures in the medulla, and the activity of sendide (the peptide based NK1RA) against cisplatin-induced emesis in the ferret.  It is likely that some peripheral exposure contributes to antiemetic effects, even if through vagal terminals in the clinical setting.