Involvement of substance P and the NK-1 receptor in pancreatic cancer

Table 1 Technical features of NK-1 receptor antagonists

NK-1 receptor antagonists	Feature
Therapeutic action	Linked to stereochemical features (receptor affinity) and not to chemical composition
Cell specificity	Specific cytotoxicity against pancreatic cancer cells via the NK-1 receptor
Antitumor action	Mitogenesis inhibition Cell death by apoptosis Angiogenesis inhibition Inhibition of the migration of cancer cells: Inhibit invasion, infiltration and metastasis
Beneficial effects	Central nervous system:
	Antiemetic
	Anxiolytic
	Antimigraine
	Anticonvulsant
	Neuroprotector
	Peripheral nervous system:
	Neuroprotector
	Liver:
	Hepatoprotector
	Kidney:
	Nephroprotector
	Systemic:
	Analgesic
	Antiinflammatory
	Antiviral
Side-effects	Headaches, hiccupping, vertigo and drowsiness
Synergistic effect with cytostatic and radiation therapy	Vinblastine, adriamycin, mitomycin, ifosfamide, cisplatin
Decrease cytostatic and radiation therapy side-effects	Cisplatin, cyclophosphamide
Block multiple intracellular signaling pathways	NK-1 receptor (G protein-coupled receptor): Rho-Rock-pMLC: Cell migration inhibition PLC-IP3-Akt: Apoptotic effect PLC-DAG-TK-MAPKs: Inhibition of tumor cell proliferation PLC-DAG-PKC-MAPKs: Inhibition of tumor cell proliferation ATP-cAMP-PKA-Phosphorylation PLA-Arachidonic acid-PGs TXAs LXs Glycogen breakdown inhibition (counteract the Warburg effect)
Dosage	Act at μmol/L in a concentration-dependent manner

Akt: Protein kinase B; ATP: Adenosine triphosphate; cAMP: Cyclic adenosine monophosphate; DAG: Diacilglicerol; IP3: Inositol triphosphate; LXs: Leukotrienes; MAPKs: Mitogen-activated protein kinase; PGs: Prostacyclin; PKA: Protein kinase A; PKC: Protein kinase C; PLA: Phospholipase A; PLC: Phospholipase C; pMLC: Myosin regulatory light chain phosphorylation; TK: Tyrosine-kinase; TXAs: Thromboxanes.