Mechanism of action Vomiting is caused when impulses from the chemoreceptor trigger zone (CRTZ) in the brain are sent to the vomiting center in the medulla. Motion sickness specifically occurs when signals to the CRTZ originate from the inner ear: motion is sensed by the fluid of the semicircular canals, which causes overstimulation. The signal travels to the brain's vestibular nuclei, then to the CRTZ, and finally to the vomiting center.<unk>  has a similar structure to substance P, the key neurotransmitter in causing vomiting, which allows it to act as an antagonist and bind to the substance P receptor neurokinin 1 (NK1). It is highly selective for NK1 over NK2 and NK3.<unk>  binds to the neurokinin receptors in the vagus nerves leaving the GI tract, as well as to receptors in the CRTZ and the vomiting center. By virtue of working at the last step in triggering vomiting, it can prevent a broader range of stimuli than most antiemetics can. It is effective against emetogens that act at the central nervous system (such as apomorphine in dogs and xylazine in cats), those that act in the periphery (e.g. syrup of ipecac), and those that act in both (e.g. cisplatin). Packaging of oral<unk>  Pharmacokinetics<unk> 's bioavailability is unaffected by the presence of food. Bioavailability is 91% at the standard subcutaneous dose but 24% at the standard oral dose; the standard oral dose is higher to partially compensate for incomplete bioavailability. It binds to plasma proteins at a rate of 99.5%; it has a low volume of distribution (9 L/kg) and is thus not extensively absorbed. Subcutaneously administered<unk>  had peak plasma concentration around half an hour after administration; the mean half-life is 6–8 hours, and a single dose lasts 24 hours in dogs. Orally administered<unk>  reached its peak plasma concentration within two hours.<unk>  undergoes 1st-pass metabolism by liver enzymes, mainly CYP2D15 (which has high affinity for<unk>  and clears over 90% of it) but also by the lower-affinity CYP3A12. Repeat dosing of<unk>  eventually saturates CYP2D15, causing the drug to accumulate due to reduced clearance. Thus, it is recommended to not use<unk>  for more than five days straight, and to have a two-day rest period to allow<unk>  to clear the body to prevent accumulation.<unk>  has over 21 metabolites, though its major one (produced by hydroxylation) is CJ-18,518.<unk>  clearance is slower in cats.
Maropitant
Lemborexant
Nefopam
Avacopan
Tofisopam
Verapamil
Fenoldopam
Alvimopan