Cisplatin-evoked emesis is predominantly due to release of serotonin and substance P (SP) in the gut and the brainstem which subsequently stimulate their corresponding 5-HT<sub>3</sub>-and neurokinin NK<sub>1</sub>-receptors to induce vomiting.
The antiemetics recommended in these guidelines (5-hydroxytryptamine type 3 receptor antagonists, neurokinin-1 receptor antagonists, dexamethasone) have significantly reduced emesis but not nausea.
LMN-NKA unexpectedly activated NK1 receptors at doses that stimulated voiding, causing emesis and hypotension that may limit the clinical utility of nonselective NK2 receptor agonists.
Serotonin (5-HT) and substance P immunostaining revealed FPL64176-induced emesis was accompanied by an increase in 5-HT but not SP-immunoreactivity in the dorsomedial subdivision of the NTS.
The latter led to identification of selective 5-HT<sub>3</sub> receptor antagonists (e.g., granisetron), a major breakthrough in treatment of chemotherapy-induced emesis; (v) <i>Neurokinin</i><sub>1</sub><i>receptor antagonists</i>-antagonists of the actions of substance P were developed as analgesics but pre-clinical studies identified broad-spectrum anti-emetic effects; clinical studies showed particular efficacy in the delayed phase of chemotherapy-induced emesis.
According to current ESMO - MASCC guidelines, a combination of a neurokinin-1 receptor antagonist (NK1RA), dexamethasone and a 5-HT3 receptor antagonist (5-HT3RA) is recommended to prevent carboplatin-induced emesis, albeit with moderate level of confidence and not unanimous consensus.
Netupitant and rolapitant are second-generation neurokinin-1 receptor antagonists that provide effective prophylaxis against delayed chemotherapy-induced vomiting and also have an antinausea benefit.
Knowledge of the involvement of the neurokinin substance P in emesis has led to the development of the neurokinin-1 receptor antagonists (NK-1 RAs) for control of chemotherapy-induced nausea and vomiting (CINV), in combination with serotonin type 3 receptor antagonists and corticosteroids.
The introduction of second generation serotonin 5-HT<sub>3</sub> receptor (5-HT<sub>3</sub>) antagonist palonosetron combined with long-acting substance P neurokinin NK<sub>1</sub> receptor (NK<sub>1</sub>) antagonists (e.g. netupitant) has substantially improved antiemetic therapy against early- and delayed-phases of emesis caused by highly emetogenic chemotherapeutics such as cisplatin.
This study was undertaken to further establish Cryptotis parva as an emesis model, by sequencing and characterizing SP mRNA, and then comparing the least shrew tachykininergic system to other mammalian species (vomiting and non-vomiting).