Big dynorphin is an endogenous opioid peptide of the dynorphin family that is composed of both dynorphin A and dynorphin B. It is derived from the precursor protein prodynorphin, encoded by the PDYN gene. Big dynorphin is notable for its potent activity at opioid receptors and its role in modulating pain, stress, emotion, and neurophysiological functions such as learning and memory. Big dynorphin has the amino acid sequence: Tyr-Gly-Gly-Phe-Leu-Arg-Arg-Ile-Arg-Pro-Lys-Leu-Lys-Trp-Asp-Asn-Gln-Lys-Arg-Tyr-Gly-Gly-Phe-Leu-Arg-Arg-Gln-Phe-Lys-Val-Val-Thr. It has nociceptive and anxiolytic-like properties, as well as effects on memory in mice.

Big dynorphin is a principal endogenous, agonist at the human kappa-opioid receptor.

Big dynorphin primarily acts as an agonist at κ-opioid receptors, where it exhibits high potency and efficacy, leading to analgesic, dysphoric, and sedative effects. Additionally, evidence suggests it may also interact with NMDA (N-methyl-D-aspartate) receptors independently of opioid pathways, contributing to effects on synaptic plasticity and neurotoxicity.

Research has implicated big dynorphin in a variety of physiological processes:

Big dynorphin levels are altered in several neuropsychiatric and neurodegenerative conditions: