DAMGO

DAMGO is a selective peptide agonist of the µ-opioid receptor (Ki = 1.18, 1430, and 213 nM for human µ-, δ-, and κ-opioid receptors, respectively) [1].

Opioid receptors are members of the class A family of G protein-coupled receptors (GPCRs), which transduce signals via heterotrimeric G proteins on the inner surface of the plasma membrane, leading to intracellular signaling cascades involved in many aspects of cellular function. Four opioid receptor types exist [μ, δ, κ, and opioid receptor-like 1 (ORL1)], among which the μ-opioid receptor has been most explored as its agonists are used to treat chronic pain [2].

In C6μ cell membranes, DAMGO at 10 µM produced a 250% stimulation of [³⁵S]GTPγS binding above basal activity through the µ-opioid receptors, with an EC50 of 222 nM [2]. In mouse vas deferens (MVD), DAMGO strongly inhibited the electrically-evoked MVD muscle contractions in concentration dependent manner, with EC50 value of 238.47 nM [3].

In the rat late permanent visceral pain model, DAMGO produced dose-dependent antinociceptive action, with potency similar to that of morphine when given i.p. to the same site where acetic acid was injected. The calculated ED50 values were 238.57 nmol/kg for morphine and 289.52 nmol/kg for DAMGO [4].

References:

[1]. Zhao G M, Qian X, Schiller P W, et al. Comparison of [Dmt¹]DALDA and DAMGO in binding and G protein activation at µ, δ, and κ opioid receptors. Journal of Pharmacology and Experimental Therapeutics, 2003, 307(3): 947-954.

[2]. Burford N T, Clark M J, Wehrman T S, et al. Discovery of positive allosteric modulators and silent allosteric modulators of the μ-opioid receptor. Proceedings of the National Academy of Sciences of the United States of America, 2013, 110(26): 10830-10835.

[3]. Lacko E, Varadi A, Rapavi R, et al. A novel µ-opioid receptor ligand with high in vitro and in vivo agonist efficacy. Current Medicinal Chemistry, 2012, 19(27): 4699-4707.

[4]. Al-Khrasani M, Lackó E, Riba P, et al. The central versus peripheral antinociceptive effects of μ-opioid receptor agonists in the new model of rat visceral pain. Brain Research Bulletin, 2012, 87(2-3): 238-243.