SP is synthesized by neurons and transported to synaptic vesicles ; the release of SP is accomplished through the depolarizing action of calcium-dependent mechanisms.  When NK 1 receptors are stimulated, they can generate various second messengers , which can trigger a wide range of effector mechanisms that regulate cellular excitability and function. One of those three well-defined, independent second messenger systems is stimulation, via phospholipase C , of phosphatidyl inositol, turnover leading to Ca mobilization from both intra- and extracellular sources. Second is the arachidonic acid mobilization via phospholipase A2 and third is the cAMP accumulation via stimulation of adenylate cyclase.  It has also been reported that SP elicits interleukin-1 (IL-1) production in macrophages, it is known to sensitize neutrophils and enhance dopamine release in the substantia nigra region in cat brain. From spinal neurons, SP is known to evoke release of neurotransmitters like acetylcholine , histamine and GABA . It is also known to secrete catecholamines and play a role in the regulation of blood pressure and hypertension. Likewise, SP is known to bind to N-methyl-D-aspartate (NMDA) receptors by eliciting excitation with calcium ion influx, which further releases nitric oxide. Studies in frogs have shown that SP elicits the release of prostaglandin E 2 and prostacyclin by the arachidonic acid pathway, which leads to an increase in corticosteroid output. 
Breakthrough CINV: Breakthrough CINV is nausea and vomiting that occurs despite antiemetic therapy. It is managed with rescue medications such as dopamine receptor antagonists (., metoclopramide, prochlorperazine, haloperidol), benzodiazepines (., lorazepam), 5-HT 3 receptor antagonists, cannabinoids (., nabilone, dronabinol, levonantradol), or novel agents (., olanzapine). Dopamine receptor antagonists’ side effects include sedation, orthostatic hypotension, and increased risk of extrapyramidal effect. The cannabinoids act against the CB1 receptor and are associated with dry mouth, ataxia, dizziness, sedation, confusion, distortion of perception, and mood changes (., euphoria, dysphoria).