opioid withdrawal

SC-17599 exhibits dose-dependent analgesic effects in both the acetic acid-induced writhing test and the hot-water tail withdrawal test. This compound also induces a Straub tail reaction in a dose-dependent and naltrexone-sensitive manner, akin to morphine. However, unlike morphine, high doses of SC-17599 do not affect motor activity. Overall, SC-17599 demonstrates selective μ-opioid receptor agonism, showing behavior effects similar to morphine, with some differences.

MOR modulator-1 (compound 6) is a potent and selective modulator of the μ opioid receptor (MOR). Compared to NAT (6α-configuration), MOR modulator-1 demonstrates improved opioid receptor selectivity, enhanced antagonistic effects in vivo, and overall reduced withdrawal symptoms. It connects to the μ, δ, and γ receptors with carboxamide linkers, showing Ki values of 0.25, 41.1, and 1.30 nM respectively.

β-Endorphin (1-27) is an endogenous peptide that binds to μ-, δ-, and κ-opioid receptors (Kis = 5.31, 6.17, and 39.82 nM, respectively, in COS-1 cells expressing rat receptors). It binds to rat and mouse brain membrane preparations (IC50s = 1.1 and 5.7 nM, respectively) and induces chemotaxis of human monocytes in vitro when used at a concentration of 1 nM. Intracerebroventricular administration of β-endorphin (1-27) increases the latency to tail withdrawal in response to thermal stimulation in mice with a median antinociceptive dose (AD50) of 1,500 pmol per animal. It inhibits antinociception induced by β-endorphin in mice in response to thermal stimuli when administered at a dose of 65 pmol per animal. In rats, β-endorphin (1-27) does not affect drug-associated place preference when administered at doses up to 20 μg, i.c.v., but inhibits β-endorphin-induced place preference when administered at a dose of 10 μg per animal.

Dapiprazole Hydrochloride (Glamidolo Hydrochloride) is an alpha-1-adrenergic antagonist that acts by blocking alpha-adrenergic receptors in the smooth muscle of blood vessels (arteries, arterioles and veins), gastrointestinal tract, and radial smooth muscle of the iris.

UFP101 is a synthetic peptide that functions as an antagonist of the nociceptin receptor, demonstrating high affinity with a Ki of 0.06 nM in CHO cells expressing the human receptor. It exhibits selectivity for the nociceptin receptor over the κ-opioid receptor, with a Ki of 204 nM in CHO cells expressing the rat receptor. The compound effectively inhibits GTPγS release from the nociceptin receptor in CHO cell membranes, with an EC50 of 1.86 nM. When administered intracerebroventricularly at a dose of 10 nmol/animal, UFP101 prolongs the latency to tail withdrawal in the tail-flick test in mice, indicating its potential as an analgesic. Additionally, at doses of 0.003, 0.03, and 0.3 mg/kg, UFP101 enhances survival in a sepsis mouse model induced by cecal ligation and puncture, suggesting potential therapeutic applications in sepsis management.

Mitraciliatine, an alkaloid discovered in M. speciosa (Kratom in Thai), acts as a partial agonist for the μ-opioid receptor (MOR) and an agonist for the κ-opioid receptor (KOR), demonstrating selectivity for these receptors over the δ-opioid receptor (DOR) with EC50 values of 228, 218, and >1,000 nM respectively in mouse receptors through a GTPγS binding assay. When administered intracerebroventricularly (i.c.v.) at 100 nmol/animal, mitraciliatine increases latency to withdrawal in the warm water tail withdrawal assay in mice, an effect reversable by MOR knockout but unaffected by KOR knockout, distinguishing it from morphine by not causing hyperlocomotion or respiratory depression.

EG-2184 is a Pannexin-1 channel inhibitor utilized in research related to opioid withdrawal.