"Endomorphin-1"

Antiallodynic Effects of Endomorphin-1 and Endomorphin-2 in the Spared Nerve Injury Model of Neuropathic Pain in Mice. The spared nerve injury (SNI) model is a new animal model that can mimic several characteristics of clinical neuropathic pain. Opioids are recommended as treatment of neuropathic pain. Therefore, the present study was conducted to investigate the antinociceptive effects of endomorphin-1 (EM-1) and endomorphin-2 (EM-2) given centrally and peripherally in the SNI model of neuropathic pain in mice. The SNI model was made in mice by sparing the sural nerve intact, when the other 2 of 3 terminal branches of the sciatic nerve (common peroneal and tibial nerves) were tightly ligated and cut. Von Frey monofilaments were used to measure the SNI-induced mechanical allodynia-like

Experimental Gene Therapy with Serine-Histogranin and Endomorphin 1 for the Treatment of Chronic Neuropathic Pain The insufficient pain relief provided by current pharmacotherapy for chronic neuropathic pain is a serious medical problem. The enhanced glutamate signaling via NMDA receptors appears to be one of the key events in the development of chronic pain. Although effective, clinical use

Infusion of endomorphin-1 (EM-1) in the MPOA and the Me modulate sexual and socio-sexual behavior in the male rat. Several neurotransmitters, among them neuropeptides, have been implicated in the control of male sexual behavior. Opioids are involved in mediating the positive affective states generated by the execution of sexual behavior in both males and females. We have previously shown that intracerebroventricular administration of endomorphin-1 (EM-1), the specific ligand for the μ opioid receptor, increased the ejaculation latency and interintromission interval and reduced the number of ejaculations during the test. In the present study we evaluated the effect of EM-1 upon male sexual behavior and socio-sexual interactions when infused in the medial preoptic area (MPOA) or the medial amygdala (Me

and unique family of endogenous opioid peptides (endomorphins) have provided a pathway for dissociating analgesia from opioid-related adverse events and developing new classes of mu-opioid receptor agonists that use biased signaling and/or target novel sites to produce analgesia with reduced side effect liability. Endomorphin-1 and -2 are endogenous opioid peptides highly selective for mu-opioid receptors that exhibit potent analgesia with reduced side effects. CYT-1010 is a cyclized, D-lysine-containing analog of endomorphin-1 with a novel mechanism of action targeting traditional mu- and exon 11/truncated mu-opioid receptor 6TM variants. CYT-1010 preclinical data have demonstrated reduced abuse potential and analgesic potency exceeding that of morphine. In an initial phase 1 clinical study, CYT-1010

with endomorphin-1, naloxone, and levetiracetam, were used in the presence of high glucose concentration in the medium to restore the cells. Glutamate-, 5-HT-, and ATP-evoked intracellular Ca release, Na/K-ATPase expression, expression of inflammatory receptors, and release of tumor necrosis factor alpha were measured. Sildenafil in ultralow concentration together with 1α,25-Dihydroxyvitamin D3 showed most prominent effects on the ATP-evoked intracellular Ca release. The μ-opioid agonist endomorphin-1, the μ-opioid antagonist naloxone in ultralow concentration, and the antiepileptic agent levetiracetam downregulated the glutamate-evoked intracellular Ca release and TLR4. The combination of the pharmaceutical substances in high glucose concentration downregulated the glutamate- and ATP-evoked Ca signaling

acute and chronic pain at the spinal level, their preemptive analgesic effects remain to be determined. In this study, we evaluated the anti-allodynic activities of endomorphins and explored their mechanisms of action after preemptive administration in a mouse model of inflammatory pain. The anti-allodynic activities of preemptive intrathecal administration of endomorphin-1 and endomorphin-2 were

are also released by primary afferents under ischaemic conditions. We examined whether high affinity mu opioid receptor (MOR) agonists, endomorphin-1 (E-1) and -2 (E-2), modulate ASIC currents and the lactic acid-mediated pressor reflex. In rat dorsal root ganglion (DRG) neurons, exposure to E-2 in acidic solutions significantly potentiated ASIC currents when compared to acidic solutions alone

with the process from pre-DM to NGR, while twenty two metabolites related to amino acid metabolism, glycerophospholipid metabolism and mitochondrial β-oxidation played important roles in the progression to DM. Results from stepwise logistic regression analysis showed that five biomarkers (20-Hydroxy-leukotriene E4, Lysopc(20:4), 5-methoxytryptamine, Endomorphin-1, Lysopc(20:3)) were good prediction

agonist endomorphin-1, and a cross-antagonism, by which a MOR antagonist counteracted MAPK activation induced by galanin. These specific interactions, which represented biochemical properties of the MOR-Gal1R heteromer, could then be identified in situ in slices of rat ventral tegmental area (VTA) with MAPK activation and two additional cell signaling pathways, AKT and CREB phosphorylation. Furthermore , in vivo microdialysis experiments showed that the disruptive peptide selectively counteracted the ability of galanin to block the dendritic dopamine release in the rat VTA induced by local infusion of endomorphin-1, demonstrating a key role of MOR-Gal1R heteromers localized in the VTA in the direct control of dopamine cell function and their ability to mediate antagonistic interactions between MOR

for analgesia, whereas IBNtxA (3'-iodobenzyol-6β-naltrexamide) needs only truncated 6TM variants. A set of endomorphin analogs fall into a third group that requires both 6TM and 7TM splice variants. Unlike morphine, endomorphin 1 and 2, DAPP (Dmt,d-Ala-Phe-Phe-NH), and IDAPP (3'-iodo-Dmt-d-Ala-Phe-Phe-NH) analgesia was lost in an exon 11 knockout mouse lacking 6TM variants. Restoring 6TM variant expression

)-enkephalin (DAMGO), a representative MOR agonist, at a low concentration and inhibited it at a higher concentration. Ignavine also exerted positive modulatory activity for DAMGO, endomorphin-1 and morphine in cAMP assay. Additionally, ignavine alone showed an analgesic effect in vivo. In silico simulation analysis suggested that ignavine would induce a unique structural change distinguished from those

Inducible expression of endomorphins in murine dendritic cells Bone marrow precursor cells were extracted from C57BL/6J mice aged 7-8 weeks, and dendritic cells were purified using anti-CD11c (a specific marker for dendritic cells) antibody-coated magnetic beads. Immunofluorescence staining revealed that the expression levels of endomorphin-1 and endomorphin-2 were upregulated in dendritic cells activated by lipopolysaccharide. An enzyme immunoassay showed that lipopolysaccharide and other Toll-like receptor ligands promoted the secretion of endomorphin-1 and endomorphin-2 from activated dendritic cells. [(3)H]-thymidine incorporation demonstrated that endomorphin-1 and endomorphin-2 both inhibited the proliferation of T lymphocyte induced by activated dendritic cells. Furthermore

The antinociceptive potencies and interactions of endogenous ligands during continuous intrathecal administration: adenosine, agmatine, and endomorphin-1. Recently, a series of endogenous ligands related to inhibition of sensory transduction of noxious stimuli at the spinal level has been described, including endomorphins, agmatine, and adenosine, which act on different receptors; however , little data exist concerning their effect during continuous administration or their interactions. In this study, we investigated the antinociceptive properties of continuously administered (for 60 min) adenosine and agmatine on carrageenan-induced thermal hyperalgesia by means of a thermal paw withdrawal test in awake rats. The possible interaction between endomorphin-1 and adenosine or agmatine

Nifedipine potentiates the antinociceptive effect of endomorphin-1 microinjected into the periaqueductal gray in rats. Endomorphin-1 is a novel endogenous mu-opioid ligand. We investigated the antinociceptive interaction between endomorphin-1 and nifedipine, an L-type calcium channel blocker, microinjected into the midbrain ventrolateral periaqueductal gray (vPAG), using the spinally-organized tail-flick test and the supraspinally-organized tail-pressure test in rats. Sprague-Dawley rats were stereotaxically implanted with a guide cannula lowered into the vPAG. Microinjection of endomorphin-1 into the vPAG led to dose-related increases in antinociceptive responses in the tail-flick test and tail-pressure test. Pretreatment with the mu-opioid receptor-selective antagonist beta

The spinal antinociceptive effects of endomorphins in rats: behavioral and G protein functional studies. Endomorphin-1 and endomorphin-2 are endogenous peptides that are highly selective for mu-opioid receptors. However, studies of their functional efficacy and selectivity are controversial. In this study, we systematically compared the effects of intrathecal (i.t.) administration of endomorphin activity at the level of the receptor-G protein in both spinal cord and thalamic membranes. In addition, antagonists selective for each receptor type were used to verify the functional selectivity of endomorphins in the rat spinal cord. After i.t. administration, endomorphin-1 and -2 produced less antinociceptive effects than DAMGO in the model of acute pain. Concentration-response curves for DAMGO

antagonist exendin(9-39) after intranasal administration. J Pharmacol Exp Ther, 2004. 309(2): p. 469-75.8. Westin, et al., Direct nose-to-brain transfer of morphine after nasal administration to rats. Pharm Res, 2006. 23(3): p. 565-72.9.Cros, C. D., I. Toth, et al. (2014). "Delivery of a lactose derivative of endomorphin 1 to the brain via the olfactory epithelial pathway." Bioorg Med Chem Lett 24(5): 1373

The peripheral antinociceptive effects of endomorphin-1 and kynurenic acid in the rat inflamed joint model. Several data suggest that both opioid and N-methyl-d-aspartate (NMDA) receptors are localized at the peripheral level, and drugs acting on these receptors may produce antinociception after topical administration; however, the antinociceptive effect of endogenous ligands at these receptors is poorly clarified. Our goal in this study was to determine the antinociceptive potency of the endogenous opioid peptide, endomorphin-1 (EM1), and the endogenous NMDA receptor antagonist, kynurenic acid (KYNA), and their interaction at the peripheral level in the rat inflamed joint model. Mechanical hypersensitivity was produced by injection of carrageenan (300 microg/20 microL) into the tibiotarsal

Chronic arthritis down-regulates peripheral mu-opioid receptor expression with concomitant loss of endomorphin 1 antinociception. To determine whether peripheral administration of the endogenous mu-opioid peptide endomorphin 1 could reduce knee joint pain, using animal models of acute and chronic arthritis. Extracellular electrophysiologic recordings were made of rat knee joint primary afferent nerve activity in response to noxious hyperrotation of the joint. Neuronal activity was assessed before and following local injection of endomorphin 1. Comparisons were made between normal knees and knees with adjuvant-induced monarthritis, tested at 48 hours and 1 week posttreatment. Expression of mu-opioid receptors in the dorsal root ganglia ipsilateral to the chronically inflamed joints

Antidepressant-like effect of endomorphin-1 and endomorphin-2 in mice. Endomorphin-1 (Tyr-Pro-Trp-Phe-NH(2)) and endomorphin-2 (Tyr-Pro-Phe-Phe-NH(2)) are two recently isolated mu-opioid selective peptides with a potent antinociceptive activity, involved in a number of physiological processes, including food intake, vasomotricity, sexual behavior, as well as neuroendocrine and cardiorespiratory functions. The neuroanatomical distribution of endomorphins prompted us to study their antidepressant activity in two animal behavioral models of depression: forced-swimming and tail-suspension tests. In both tests, the intracerebroventricular (i.c.v.) injection of either endomorphin-1 or endomorphin-2 significantly decreased the duration of immobility, interpreted as an expression of 'behavioral despair