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https://www.readbyqxmd.com/read/28966276/c-homomorphinan-derivatives-as-lead-compounds-to-obtain-safer-and-more-clinically-useful-analgesics
#1
Kyoko Ishikawa, Fumika Karaki, Kaoru Tayama, Eika Higashi, Shigeto Hirayama, Kennosuke Itoh, Hideaki Fujii
Buprenorphine shows strong analgesic effects on moderate to severe pain. Although buprenorphine can be used more safely than other opioid analgesics, it has room for improvement in clinical utility. Investigation of compounds structurally related to buprenorphine should be an approach to obtain novel analgesics with safer and improved profiles compared to buprenorphine. In the course of our previous studies, we observed that derivatives obtained by cyclizing C-homomorphinans were structurally related to buprenorphine...
2017: Chemical & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28956418/protective-effects-of-smyrnium-cordifolium-boiss-essential-oil-on-pentylenetetrazol-induced-seizures-in-mice-involvement-of-benzodiazepine-and-opioid-antagonists
#2
N Abbasi, S Mohammadpour, E Karimi, A Aidy, P Karimi, M Azizi, K Asadollahi
Smyrnium cordifolium as a wild plant is used in traditional medicine in Iran for the treatment of anxiety and insomnia. The anticonvulsant effect of this plant has not been studied to date, therefore this study aimed to evaluate the anticonvulsant effects of its essential oil and curzerene on seizure. Essential oil of the Smyrnium cordifolium plant was prepared by the hydro-distillation method. Gas chromatography and gas chromatography-mass spectroscopy analysis of the essential oil revealed its main components...
July 2017: Journal of Biological Regulators and Homeostatic Agents
https://www.readbyqxmd.com/read/28944090/rapid-identification-of-buprenorphine-in-patient-saliva
#3
Stuart Farquharson, Kathryn Dana, Chetan Shende, Zachary Gladding, Jenelle Newcomb, Jessica Dascher, Ismene L Petrakis, Albert J Arias
Buprenorphine is becoming the medication of choice to help patients withdraw from opioid addiction. However, treatment is compromised by the inability of physicians to assess patient usage during scheduled examinations. Here we describe the development of a point-of-care (POC) analyzer that can rapidly measure both illicit and treatment drugs in patient saliva, ideally in the physician's office, and with a degree of accuracy similar to chromatography. The analyzer employs a relatively simple supported liquid extraction to isolate the drugs from the saliva and surface-enhanced Raman spectroscopy (SERS) to detect the drugs...
June 2017: Journal of Analytical & Bioanalytical Techniques
https://www.readbyqxmd.com/read/28877966/t-cell-mediation-of-pregnancy-analgesia-affecting-chronic-pain-in-mice
#4
Sarah F Rosen, Boram Ham, Shannon Drouin, Nadia Boachie, Anne-Julie Chabot-Dore, Jean-Sebastien Austin, Luda Diatchenko, Jeffrey S Mogil
It has been consistently reported that many female chronic pain sufferers have an attenuation of symptoms during pregnancy. Rats display increased pain tolerance during pregnancy, due to an increase in opioid receptors in the spinal cord. These past studies did not consider the role of non-neuronal cells, now appreciated to play an important role in chronic pain processing. Using an inflammatory (complete Freund's adjuvant) or neuropathic (spared nerve injury) model of persistent pain, we observe that young adult female mice in early pregnancy switch from a micgrolia-independent to a microglia-dependent pain hypersensitivity mechanism...
September 6, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28857657/opioid-system-contribution-to-the-antidepressant-like-action-of-m-trifluoromethyl-diphenyl-diselenide-in-mice-a-compound-devoid-of-tolerance-and-withdrawal-syndrome
#5
Suzan G Rosa, Ana P Pesarico, Carolina F Tagliapietra, Sônia C A da Luz, Cristina W Nogueira
Animal and clinical researches indicate that the opioid system exerts a crucial role in the etiology of mood disorders and is a target for intervention in depression treatment. This study investigated the contribution of the opioid system to the antidepressant-like action of acute or repeated m-trifluoromethyl-diphenyl diselenide administration to Swiss mice. m-Trifluoromethyl-diphenyl diselenide (50 mg/kg, intragastric) produced an antidepressant-like action in the forced swimming test from 30 min to 24 h after treatment...
August 1, 2017: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/28856406/panicolytic-like-effects-caused-by-substantia-nigra-pars-reticulata-pretreatment-with-low-doses-of-endomorphin-1-and-high-doses-of-ctop-or-the-nop-receptors-antagonist-jtc-801-in-male-rattus-norvegicus
#6
Juliana Almeida da Silva, Audrey Franceschi Biagioni, Rafael Carvalho Almada, Renato Leonardo de Freitas, Norberto Cysne Coimbra
RATIONALE: Gamma-aminobutyric acid (GABA)ergic neurons of the substantia nigra pars reticulata (SNpr) are connected to the deep layers of the superior colliculus (dlSC). The dlSC, in turn, connect with the SNpr through opioid projections. Nociceptin/orphanin FQ peptide (N/OFQ) is a natural ligand of a Gi protein-coupled nociceptin receptor (ORL1; NOP) that is also found in the SNpr. Our hypothesis is that tectonigral opioid pathways and intranigral orphanin-mediated mechanisms modulate GABAergic nigrotectal connections...
August 30, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28844215/antinociceptive-and-anti-inflammatory-activities-of-leaf-extracts-from-annona-tomentosa-r-e-fr
#7
Lilian Uchoa Carneiro, Ilna Gomes da Silva, Mirian Eliza Alves de Souza, Wellington da Silva Côrtes, Mário Geraldo de Carvalho, Bruno Guimarães Marinho
OBJECTIVE: Annona tomentosa R.E.Fr is a species not endemic to Brazil that belongs to the phytogeographic areas of the Amazon, Cerrado and Pantanal. Popularly known as "araticum rasteiro" or "araticum de moita", A. tomentosa is edible and tea made from the leaves has been used as an anti-inflammatory by native communities. There is no scientific evidence for these uses of A. tomentosa, especially those related to the control of pain and inflammation. For this reason, in the present study we evaluated the antinociceptive and anti-inflammatory activities of partitions from the methanolic extract of A...
September 2017: Journal of Integrative Medicine
https://www.readbyqxmd.com/read/28838808/characterization-of-structurally-novel-g-protein-biased-cb1-agonists-implications-for-drug-development
#8
Benjamin M Ford, Lirit N Franks, Sherrica Tai, William E Fantegrossi, Edward L Stahl, Michael D Berquist, Christian V Cabanlong, Catheryn D Wilson, Narsimha R Penthala, Peter A Crooks, Paul L Prather
The human cannabinoid subtype 1 receptor (hCB1R) is highly expressed in the CNS and serves as a therapeutic target for endogenous ligands as well as plant-derived and synthetic cannabinoids. Unfortunately, acute use of hCB1R agonists produces unwanted psychotropic effects and chronic administration results in development of tolerance and dependence, limiting the potential clinical use of these ligands. Studies in β-arrestin knockout mice suggest that interaction of certain GPCRs, including μ-, δ-, κ-opioid and hCB1Rs, with β-arrestins might be responsible for several adverse effects produced by agonists acting at these receptors...
August 23, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28819330/synthesis-and-investigation-of-mixed-%C3%AE-opioid-and-%C3%AE-opioid-agonists-as-possible-bivalent-ligands-for-treatment-of-pain
#9
Ruben S Vardanyan, James P Cain, Saghar Mowlazadeh Haghighi, Vlad K Kumirov, Mary I McIntosh, Alexander J Sandweiss, Frank Porreca, Victor J Hruby
Several studies have suggested functional association between μ-opioid and δ-opioid receptors and showed that μ-activity could be modulated by δ-ligands. The general conclusion is that agonists for the δ-receptor can enhance the analgesic potency and efficacy of μ-agonists. Our preliminary investigations demonstrate that new bivalent ligands constructed from the μ-agonist fentanyl and the δ-agonist enkephalin-like peptides are promising entities for creation of new analgesics with reduced side effects for treatment of neuropathic pain...
March 2017: Journal of Heterocyclic Chemistry
https://www.readbyqxmd.com/read/28806211/the-opiorphin-analog-str-324-decreases-sensory-hypersensitivity-in-a-rat-model-of-neuropathic-pain
#10
Alain Van Elstraete, Philippe Sitbon, Leila Hamdi, Victor Juarez-Perez, Jean-Xavier Mazoit, Dan Benhamou, Catherine Rougeot
BACKGROUND: Neuropathic pain represents a therapeutic challenge, and treatments with increased efficacy and tolerability still need to be developed. Opiorphin protects endogenous enkephalins from degradation, potentiating enkephalin-dependent analgesia via the activation of opioid pathways. Enkephalins are natural ligands of opioid receptors, with strong affinity for δ-opioid receptors. Expression of functional δ-opioid receptors increases in sensory neurons after peripheral nerve injury in neuropathic pain models...
August 10, 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/28781901/enkephalins-endogenous-analgesics-with-an-emerging-role-in-stress-resilience
#11
REVIEW
Mathilde S Henry, Louis Gendron, Marie-Eve Tremblay, Guy Drolet
Psychological stress is a state of mental or emotional strain or tension that results from adverse or demanding circumstances. Chronic stress is well known to induce anxiety disorders and major depression; it is also considered a risk factor for Alzheimer's disease. Stress resilience is a positive outcome that is associated with preserved cognition and healthy aging. Resilience presents psychological and biological characteristics intrinsic to an individual conferring protection against the development of psychopathologies in the face of adversity...
2017: Neural Plasticity
https://www.readbyqxmd.com/read/28758123/peripheral-antinociception-induced-by-aripiprazole-is-mediated-by-the-opioid-system
#12
Renata Cristina Mendes Ferreira, Ana Flávia Almeida-Santos, Igor Dimitri Gama Duarte, Daniele C Aguiar, Fabricio A Moreira, Thiago Roberto Lima Romero
BACKGROUND: Aripiprazole is an antipsychotic drug used to treat schizophrenia and related disorders. Our previous study showed that this compound also induces antinociceptive effects. The present study aimed to assess the participation of the opioid system in this effect. METHODS: Male Swiss mice were submitted to paw pressure test and hyperalgesia was induced by intraplantar injection of prostaglandin E2 (PGE2, 2 μg). Aripiprazole was injected 10 min before the measurement...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28740609/simple-tetrahydroisoquinolines-are-potent-and-selective-kappa-opioid-receptor-antagonists
#13
Chad M Kormos, Pauline W Ondachi, Scott P Runyon, James B Thomas, S Wayne Mascarella, Ann M Decker, Hernán A Navarro, F Ivy Carroll
Potent and selective κ opioid receptor antagonists have been derived from the N-substituted trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidine class of pure opioid receptor antagonists. In order to determine if the 3-hydroxyphenyl and/or the piperidine amino groups are required for obtaining the pure opioid antagonists, (3R)-7-hydroxy-N-[(1S)-2-methyl-1-(piperidine-1-ylmethyl)propyl]-1,2,3,4-tetrahydroiosquinoline-3-carboxamide (1), which does not have a 4-(3-hydroxyphenyl) group, and (3R)-N-(1R)-1-(cyclohexylmethyl)-2-methylpropyl]-7-hydroxy-1,2,3,4-tetrahydroisoquinoline-3-carboxamide (2), which does not have a 4-hydroxylphenyl or a piperidine amino group, were synthesized and evaluated for their [(35)S]GTPγS binding properties at the μ, δ, and κ opioid receptors...
July 13, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28726190/effect-of-peripheral-%C3%AE-%C3%AE-and-%C3%AE%C2%BA-opioid-ligands-on-the-development-of-tolerance-to-ethanol-induced-analgesia
#14
S K Sudakov, E V Alekseeva, G A Nazarova
We studied the rate of development of tolerance to the ethanol-induced analgesia under the effect of μ-, δ-, and κ-opioid agonists and antagonists not crossing the blood-brain barrier and rapidly inactivated by gastric and duodenal proteolytic enzymes. Activation of gastric κ-opioid receptors eliminated the analgesic effect of ethanol and accelerated the development of tolerance to ethanol-induced analgesia. In contrast, activation of gastric μ-opioid receptors decelerated the development of this tolerance...
June 2017: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28700700/the-induction-of-the-transcription-factor-nrf2-enhances-the-antinociceptive-effects-of-delta-opioid-receptors-in-diabetic-mice
#15
Christina McDonnell, Sergi Leánez, Olga Pol
The involvement of heme oxygenase 1 (HO-1) in the modulation of the antinociceptive effects of opioids in type 1 diabetes has been demonstrated but the role played by the transcription factor Nrf2 in the regulation of painful neuropathy and in the effects and expression of δ-opioid receptors (DOR) in type 2 diabetes, has not been studied. In male BKS.Cg-m+/+Leprdb/J (db/db) mice, the anti-allodynic effects produced by a Nrf2 transcription factor activator, sulforaphane (SFN) administered alone and combined with two DOR agonists, [d-Pen(2),d-Pen(5)]-Enkephalin (DPDPE) and (+)-4-[(αR)-α-((2S,5R)-4-Allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N diethylbenzamide (SNC-80), were evaluated...
2017: PloS One
https://www.readbyqxmd.com/read/28673836/microneedles-enhance-topical-delivery-of-15-deoxy-%C3%AE-12-14-prostaglandin-j2-and-reduce-nociception-in-temporomandibular-joint-of-rats
#16
Cristina G Macedo, Amit K Jain, Michelle FranzMontan, Marcelo H Napimoga, Juliana T Clemente-Napimoga, Harvinder Singh Gill
The pain arising from temporomandibular disorders is often treated with opioids and agents that inhibit the immune response and are associated with substantial adverse effects and long-term risks. Thus, the development of new therapies that are safer and more effective is of great interest to patients and clinicians. 15-deoxy-Δ(12,14)-prostaglandin J2 (15d-PGJ2) is naturally produced in the human body and has anti-inflammatory properties. We have previously shown in a rat temporomandibular joint (TMJ) model that injection of 15d-PGJ2 into the rat TMJ can provide antinociceptive relief against a subsequent noxious challenge from formalin injection into the same TMJ...
June 30, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28662966/antitrichomonal-activity-of-%C3%AE-opioid-receptor-antagonists-7-benzylidenenaltrexone-derivatives
#17
Noriki Kutsumura, Yasuaki Koyama, Yasuyuki Nagumo, Ryo Nakajima, Yoshiyuki Miyata, Naoshi Yamamoto, Tsuyoshi Saitoh, Naoko Yoshida, Satoshi Iwata, Hiroshi Nagase
The 7-benzylidenenaltrexone (BNTX) derivatives 2a-v, 3a-c, 13a-c, and 14a were synthesized from naltrexone (1) and evaluated for their antitrichomonal activity. The structure-activity-relationship studies found that 4-iodo-BNTX (2g) showed the highest activity (IC50=10.5µM) and the affinity for the opioid receptor was less important for antitrichomonal activity against Trichomonas vaginalis. The morphinan skeleton bearing both the double bond for a Michael acceptor and the phenolic hydroxy group would be a specific template for development of antitrichomonal agents...
August 15, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28647729/analgesic-effects-of-diluted-bee-venom-acupuncture-mediated-by-%C3%AE-opioid-and-%C3%AE-2-adrenergic-receptors-in-osteoarthritic-rats
#18
Jeong-Eun Huh, Byung-Kwan Seo, Jung-Woo Lee, Chanyoung Kim, Yeon-Cheol Park, Jae-Dong Lee, Yong-Hyeon Baek
Context • Pain from osteoarthritis is associated with peripheral nociception and central pain processing. Given the unmet need for innovative, effective, and well-tolerated therapies, many patients, after looking for more satisfactory alternatives, decide to use complementary and alternative modalities. The analgesic mechanism of subcutaneous injections of diluted bee venom into an acupoint is thought to be part of an anti-inflammatory effect and the central modulation of pain processing. Objectives • Using the rat model of collagenase-induced osteoarthritis (CIOA), the study intended to investigate the analgesic effects of bee venom acupuncture (BVA) as they are related to the acupuncture points and dosage used and to determine whether the analgesic mechanisms of BVA for pain were mediated by opioid or adrenergic receptors...
June 23, 2017: Alternative Therapies in Health and Medicine
https://www.readbyqxmd.com/read/28647372/delta-opioid-receptor-agonist-attenuates-lipopolysaccharide-induced-myocardial-injury-by-regulating-autophagy
#19
Pin Zhao, Jianke Kuai, Jinjian Gao, Li Sun, Yan Wang, Linong Yao
BACKGROUND: Previous studies have described the protective effects of DADLE on myocardial injury in sepsis. Recently, autophagy has been shown to be an innate defense mechanism in sepsis-related myocardial injury. However, whether DADLE has an pro-autophagic effect is yet to be elucidated. The present study aimed to investigate the effect of DADLE on the regulation of autophagy during sepsis. METHODS: Male mice were subjected to LPS or vehicle intraperitoneal injection...
October 7, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28645007/activation-of-the-pi3k-akt-pathway-promotes-neuroprotection-of-the-%C3%AE-opioid-receptor-agonist-against-cerebral-ischemia-reperfusion-injury-in-rat-models
#20
Mei-Rong Lv, Bin Li, Ming-Guang Wang, Fan-Guo Meng, Jian-Jun Yu, Feng Guo, Ye Li
The central objective was to identify the role of the PI3K-Akt activation pathway on the neuroprotection of δ-opioid receptor agonist (DADLE) against cerebral ischemia-reperfusion (I/R) injury in a rat model. Fifty-five male Sprague-Dawley (SD) rats were included to establish a middle cerebral artery occlusion (MCAO) model which were then divided into the sham, MCAO, LY294002 (MCAO+DADLE+LY294002 [inhibitor of PI3K-Akt pathway]), DADLE (MCAO+DADLE) and DMSO (MCAO+DADLE+DMSO [dimethyl sulphoxide]) groups. The cerebral infarction (CI) volume and nerve cell apoptosis was determined using TTC and TUNEL staining...
September 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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