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Substance P is a neurokinin undecapeptide neurotransmitter and neuromodulator.

ChEBI: Substance P is a neuropeptide consisting of 11-amino acids. It preferentially activates neurokinin-1 receptors, exterting excitatory effects on central and peripheral neurons and involved in pain transmission. It has a role as a neurotransmitter, a vasodilator agent and a neurokinin-1 receptor agonist. It is a conjugate base of a substance P(3+).

Substance P is an 11-amino-acid neuropeptide belonging to the tachykinin family, mediating its biological actions through activation of G protein–coupled tachykinin (neurokinin-1 [NK1]) receptors. Its proposed physiological roles include inflammation, pain, GI and respiratory function, stress responses, and emesis. Substance P is uniquely associated with the monoamine neurotransmitters, 5-HT and NE.

The 5-HT neurons coexpress substance P, and the firing of NE neurons is modulated by substance P. Preclinical studies have supported a role of the substance P–NK1 receptor system in stress-related disorders, which has guided the antidepressant development of centrally active NK1 receptor antagonists, such as aprepitant. The NK1 antagonists are generally well tolerated and exhibit less nausea and sexual dysfunction than some currently used antidepressants.