MyMedR

Displaying publications 41 - 60 of 365 in total

Abstract:

Sort:

Analgesic effects of main indole alkaloid of kratom, mitragynine in acute pain animal model

Mat NH, Bakar SNS, Murugaiyah V, Chawarski MC, Hassan Z

Behav Brain Res, 2023 Feb 15;439:114251.
PMID: 36503042 DOI: 10.1016/j.bbr.2022.114251

Mitragynine exerts its analgesic effect mainly via opioid receptors activation. Additionally, the effect may be mediated via mitragynine's anti-inflammatory property and non-opioid receptor pain pathways, namely through the TRPV1 receptor. No studies identify hitherto, hence, the current study aimed to investigate the mitragynine's analgesic effect via the anti-inflammatory property, non-opioid receptor (TRPV1) and the effective dose (ED) to alleviate pain. Male and female Sprague Dawley rats were pre-treated intraperitoneally with either mitragynine (1, 5, 10, 13, 15 or 30 mg/kg), vehicle, or indomethacin (1 mg/kg) 30 min before inducing inflammatory pain using acetic acid. The writhes and pain-related withdrawal behaviour occurrence were counted within a 1-h duration. Percentage of writhes inhibition, pain-related withdrawal behaviour aggregate, ED50 and ED95 were determined. The body temperature was recorded and TRPV1 expression in the rats' brains was measured. Mitragynine (except 1 mg/kg) significantly reduced the number of writhes compared with the vehicle administered group. Mitragynine (30 mg/kg) demonstrated 99.5% inhibition of writhing behaviour and low withdrawal behaviour score compared with vehicle and indomethacin and successfully blocked the hypothermia induced by acetic acid. The overall ED50 and ED95 values of mitragynine were 3.62 and 20.84 mg/kg, respectively. The percentage of writhing inhibition and withdrawal behaviour were similar in both genders. Mitragynine (15 and 30 mg/kg) significantly reduced the TRPV1 expression in the brain of the rats. Mitragynine alleviated pain-like behaviour and showed analgesic effects via anti-inflammatory and non-opioid receptor pathways. The findings also suggest that mitragynine might regulate some physiological functions of the rat.

Matched MeSH terms: Analgesics/pharmacology
Mitragynine, a primary constituent of kratom reinstates morphine-seeking behaviour in rats

Japarin RA, Harun N, Hassan Z, Shoaib M

Behav Pharmacol, 2023 Apr 01;34(2-3):123-130.
PMID: 36752325 DOI: 10.1097/FBP.0000000000000715

Mitragynine (MG) is a pharmacologically active alkaloid derived from the leaves of Mitragyna speciosa Korth (Kratom). This plant has sparked significant interest as a potential alternative treatment for managing opioid dependence and withdrawal due to its opioid-like pharmacological effects. However, whether MG exposure would trigger opioid-seeking behaviour following abstinence has not been investigated. The present study examined the effects of MG priming on morphine-seeking behaviour in rats. Male Sprague-Dawley rats were initially trained to intravenously self-administer morphine (0.5 mg/kg/infusion) under a fixed ratio-3 schedule of reinforcement. Removal of both morphine infusions and drug-associated cues led to the subsequent extinction of the drug-seeking behaviour. Tests of reinstatement were made following exposure to a randomised order of intraperitoneal injections of MG (3, 10 and 30 mg/kg), morphine (5 mg/kg) and vehicle. Significant levels of drug-seeking behaviour were observed following extended access to morphine self-administration, which was extinguished following removal of morphine and cues indicative of morphine-seeking behaviour, supporting the relapse model. The present finding demonstrated that MG priming in a dose of 10 mg/kg resulted in the reinstatement of morphine-seeking behaviour, whereas the higher MG dose (30 mg/kg) tested suppressed the seeking response. This study indicated that exposure to a low MG dose may increase the likelihood of relapsing to opioids, suggesting that the potential of MG as a treatment for opioid management merits further scientific assessment of its ability to trigger relapse to opioid abuse.

Matched MeSH terms: Analgesics, Opioid/pharmacology
Fulltext Antinociceptive Activity of Petroleum Ether Fraction of Clinacanthus nutans Leaves Methanolic Extract: Roles of Nonopioid Pain Modulatory Systems and Potassium Channels

Zakaria ZA, Abdul Rahim MH, Roosli RAJ, Mohd Sani MH, Marmaya NH, Omar MH, et al.

Biomed Res Int, 2019;2019:6593125.
PMID: 31467905 DOI: 10.1155/2019/6593125

Methanolic extract of Clinacanthus nutans Lindau leaves (MECN) has been reported to exert antinociceptive activity. The present study aimed to elucidate the possible antinociceptive mechanisms of a lipid-soluble fraction of MECN, which was obtained after sequential extraction in petroleum ether. The petroleum ether fraction of C. nutans (PECN), administered orally to mice, was (i) subjected to capsaicin-, glutamate-, phorbol 12-myristate 13-acetate-, bradykinin-induced nociception model; (ii) prechallenged (intraperitoneal (i.p.)) with 0.15 mg/kg yohimbine, 1 mg/kg pindolol, 3 mg/kg caffeine, 0.2 mg/kg haloperidol, or 10 mg/kg atropine, which were the respective antagonist of α 2-adrenergic, β-adrenergic, adenosinergic, dopaminergic, or muscarinic receptors; and (iii) prechallenged (i.p.) with 10 mg/kg glibenclamide, 0.04 mg/kg apamin, 0.02 mg/kg charybdotoxin, or 4 mg/kg tetraethylammonium chloride, which were the respective inhibitor of ATP sensitive-, small conductance Ca2+-activated-, large conductance Ca2+-activated-, or nonselective voltage-activated-K+ channel. Results obtained demonstrated that PECN (100, 250, and 500 mg/kg) significantly (P<0.05) inhibited all models of nociception described earlier. The antinociceptive activity of 500 mg/kg PECN was significantly (P<0.05) attenuated when prechallenged with all antagonists or K+ channel blockers. However, only pretreatment with apamin and charybdotoxin caused full inhibition of PECN-induced antinociception. The rest of the K+ channel blockers and all antagonists caused only partial inhibition of PECN antinociception, respectively. Analyses on PECN's phytoconstituents revealed the presence of antinociceptive-bearing bioactive compounds of volatile (i.e., derivatives of γ-tocopherol, α-tocopherol, and lupeol) and nonvolatile (i.e., cinnamic acid) nature. In conclusion, PECN exerts a non-opioid-mediated antinociceptive activity involving mainly activation of adenosinergic and cholinergic receptors or small- and large-conductance Ca2+-activated-K+ channels.

Matched MeSH terms: Analgesics/pharmacology*; Analgesics/chemistry; Analgesics, Non-Narcotic/pharmacology; Analgesics, Non-Narcotic/chemistry
Fulltext Electroencephalographic changes associated with antinociceptive actions of lidocaine, ketamine, meloxicam, and morphine administration in minimally anaesthetized dogs

Kaka U, Hui Cheng C, Meng GY, Fakurazi S, Kaka A, Behan AA, et al.

Biomed Res Int, 2015;2015:305367.
PMID: 25695060 DOI: 10.1155/2015/305367

Effects of ketamine and lidocaine on electroencephalographic (EEG) changes were evaluated in minimally anaesthetized dogs, subjected to electric stimulus. Six dogs were subjected to six treatments in a crossover design with a washout period of one week. Dogs were subjected to intravenous boluses of lidocaine 2 mg/kg, ketamine 3 mg/kg, meloxicam 0.2 mg/kg, morphine 0.2 mg/kg and loading doses of lidocaine 2 mg/kg followed by continuous rate infusion (CRI) of 50 and 100 mcg/kg/min, and ketamine 3 mg/kg followed by CRI of 10 and 50 mcg/kg/min. Electroencephalogram was recorded during electrical stimulation prior to any drug treatment (before treatment) and during electrical stimulation following treatment with the drugs (after treatment) under anaesthesia. Anaesthesia was induced with propofol and maintained with halothane at a stable concentration between 0.85 and 0.95%. Pretreatment median frequency was evidently increased (P < 0.05) for all treatment groups. Lidocaine, ketamine, and morphine depressed the median frequency resulting from the posttreatment stimulation. The depression of median frequency suggested evident antinociceptive effects of these treatments in dogs. It is therefore concluded that lidocaine and ketamine can be used in the analgesic protocol for the postoperative pain management in dogs.

Matched MeSH terms: Analgesics/pharmacology*
Mechanisms of α-mangostin-induced antinociception in a rodent model

Sani MH, Taher M, Susanti D, Kek TL, Salleh MZ, Zakaria ZA

Biol Res Nurs, 2015 Jan;17(1):68-77.
PMID: 25504952 DOI: 10.1177/1099800414529648

Elucidate the antinociceptive mechanisms of α-mangostin isolated from Garcinia malaccensis Linn.

Matched MeSH terms: Analgesics/pharmacology*
Antinociceptive and antiedematogenic activities of andrographolide isolated from Andrographis paniculata in animal models

Sulaiman MR, Zakaria ZA, Abdul Rahman A, Mohamad AS, Desa MN, Stanslas J, et al.

Biol Res Nurs, 2010 Jan;11(3):293-301.
PMID: 19689990 DOI: 10.1177/1099800409343311

The current study was performed to evaluate the antinociceptive and antiedematogenic properties of andrographolide isolated from the leaves of Andrographis paniculata using two animal models. Antinociceptive activity was evaluated using the acetic acid- induced writhing and the hot-plate tests, while antiedematogenic activity was measured using the carrageenan-induced paw edema test. Subcutaneous (s.c.) administration of andrographolide (10, 25, and 50 mg/kg) did not affect the motor coordination of the experimental animals but produced significant (p < .05) antinociceptive activity when assessed using both tests. However, 2 mg/kg naloxone failed to affect the 25 mg/kg andrographolide activity in both tests, indicating that the activity was modulated via nonopioid mechanisms. Furthermore, andrographolide showed significant (p < .05) antiedematogenic activity. In conclusion, the results obtained suggest that andrographolide has antinociceptive and antiedematogenic activities; it may be useful for treating pain and inflammation once human studies are conducted.

Matched MeSH terms: Analgesics/isolation & purification; Analgesics/pharmacology; Analgesics/therapeutic use*
Fulltext The intraperitoneal ondansetron for postoperative pain management following laparoscopic cholecystectomy: A proof-of-concept, double-blind, placebo-controlled trial

Abdelaziz DH, Boraii S, Cheema E, Elnaem MH, Omar T, Abdelraouf A, et al.

Biomed Pharmacother, 2021 Aug;140:111725.
PMID: 34015580 DOI: 10.1016/j.biopha.2021.111725

BACKGROUND: Pain after laparoscopic cholecystectomy remains a major challenge. Ondansetron blocks sodium channels and may have local anesthetic properties.
AIMS: To investigate the effect of intraperitoneal administration of ondansetron for postoperative pain management as an adjuvant to intravenous acetaminophen in patients undergoing laparoscopic cholecystectomy.
METHODS: Patients scheduled for elective laparoscopic cholecystectomy were randomized into two groups (n = 25 each) to receive either intraperitoneal ondansetron or saline injected in the gall bladder bed at the end of the procedure. The primary outcome was the difference in pain from baseline to 24-h post-operative assessed by comparing the area under the curve of visual analog score between the two groups.
RESULTS: The derived area under response curve of visual analog scores in the ondansetron group (735.8 ± 418.3) was 33.97% lower than (p = 0.005) that calculated for the control group (1114.4 ± 423.9). The need for rescue analgesia was significantly lower in the ondansetron (16%) versus in the control group (54.17%) (p = 0.005), indicating better pain control. The correlation between the time for unassisted mobilization and the area under response curve of visual analog scores signified the positive analgesic influence of ondansetron (rs =0.315, p = 0.028). The frequency of nausea and vomiting was significantly lower in patients who received ondansetron than that reported in the control group (p = 0.023 (8 h), and 0.016 (24 h) respectively).
CONCLUSIONS: The added positive impact of ondansetron on postoperative pain control alongside its anti-emetic effect made it a unique novel option for patients undergoing laparoscopic cholecystectomy.

Matched MeSH terms: Analgesics/therapeutic use*
Fulltext Effects of nerol on paracetamol-induced liver damage in Wistar albino rats

Islam MT, Quispe C, Islam MA, Ali ES, Saha S, Asha UH, et al.

Biomed Pharmacother, 2021 Aug;140:111732.
PMID: 34130201 DOI: 10.1016/j.biopha.2021.111732

Nerol, a monoterpene is evident to possess diverse biological activities, including antioxidant, anti-microbial, anti-spasmodic, anthelmintic, and anti-arrhythmias. This study aims to evaluate its hepatoprotective effect against paracetamol-induced liver toxicity in a rat model. Five groups of rats (n = 7) were orally treated (once daily) with 0.05% tween 80 dissolved in 0.9% NaCl solution (vehicle), paracetamol 640 mg/kg (negative control), 50 mg/kg silymarin (positive control), or nerol (50 and 100 mg/kg) for 14 days, followed by the hepatotoxicity induction using paracetamol (PCM). The blood samples and livers of the animals were collected and subjected to biochemical and microscopical analysis. The histological findings suggest that paracetamol caused lymphocyte infiltration and marked necrosis, whereas maintenance of the normal hepatic structural was observed in group pre-treated with silymarin and nerol. The rats pre-treated with nerol significantly and dose-dependently reduced the hepatotoxic markers in animals. Nerol at 100 mg/kg significantly reversed the paracetamol-induced altered situations, including the liver enzymes, plasma proteins, antioxidant enzymes and serum bilirubin, lipid peroxidation (LPO) and cholesterol [e.g., total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c)] levels in animals. Taken together, nerol exerted significant hepatoprotective activity in rats in a dose-dependent manner. PCM-induced toxicity and nerol induced hepatoprotective effects based on expression of inflammatory and apoptosis factors will be future line of work for establishing the precise mechanism of action of nerol in Wistar albino rats.

Matched MeSH terms: Analgesics, Non-Narcotic*
Fulltext Methanol Extract of Dicranopteris linearis Leaves Attenuate Pain via the Modulation of Opioid/NO-Mediated Pathway

Zakaria ZA, Roosli RAJ, Marmaya NH, Omar MH, Basir R, Somchit MN

Biomolecules, 2020 02 12;10(2).
PMID: 32059475 DOI: 10.3390/biom10020280

Dicranopteris linearis leaf has been reported to exert antinociceptive activity. The present study elucidates the possible mechanisms of antinociception modulated by the methanol extract of D. linearis leaves (MEDL) using various mouse models. The extract (25, 150, and 300 mg/kg) was administered orally to mice for 30 min priot to subjection to the acetic acid-induced writhing-, hot plate- or formalin-test to establish the antinociceptive profile of MEDL. The most effective dose was then used in the elucidation of possible mechanisms of action stage. The extract was also subjected to the phytochemical analyses. The results confirmed that MEDL exerted significant (p < 0.05) antinociceptive activity in those pain models as well as the capsaicin-, glutamate-, bradykinin- and phorbol 12-myristate 13-acetate (PMA)-induced paw licking model. Pretreatment with naloxone (a non-selective opioid antagonist) significantly (p < 0.05) reversed MEDL effect on thermal nociception. Only l-arginine (a nitric oxide (NO) donor) but not N(ω)-nitro-l-arginine methyl ester (l-NAME; a NO inhibitor) or 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; a specific soluble guanylyl cyclase inhibitor) significantly (p < 0.05) modified MEDL effect on the writhing test. Several polyphenolics and volatile antinociceptive compounds were detected in MEDL. In conclusion, MEDL exerted the opioid/NO-mediated antinociceptive activity, thus, justify D. linearis as a potential source for new analgesic agents development.

Matched MeSH terms: Analgesics/pharmacology*; Analgesics, Opioid/metabolism*
Fulltext Knee tuberculosis: a challenge in diagnosis and treatment

Muhammad Wafiuddin, Ahmad Faizal Roslan, Ahmad Hafiz Zulkifly

Borneo Journal of Medical Sciences, 2021;15(1):37-43.
MyJurnal

Tuberculosis (TB) is an ancient disease dated back from ancient Greece time. Once rare in developed countries, now it has re-emerged due to immigration and secondary immunodeficiency. A 27-year-old lady had left knee pain for the past 4 years, went for knee diagnostic arthroscopy procedure, and diagnosed as pigmented villonodular synovitis (PVNS) of the left knee. Despite regular analgesics and physiotherapy, patient symptoms worsen. Two years after the initial treatment, the patient went for a further workout and diagnosed as knee tuberculosis, commenced on anti-TB treatment, the patient still left complicated with a stiff knee and fixed flexion deformity. Identification of knee tuberculosis during the initial phase is crucial as late diagnosis and treatment will leave the patient with debilitating complications.

Matched MeSH terms: Analgesics
Fulltext Accidental self-injection of Xylazine during work: a rare case

Ganapathy, Ganesh Kumar, Dharmalingam, T. Kumaravadivel, Sathival, Mugunthan M.

Borneo Journal of Medical Sciences, 2018;12(2):47-49.
MyJurnal

Xylazine is an alpha-2agonist often used as a sedative, analgesic and muscle relaxant agent
in animals. Xylazine was not accepted by Food and Drug Administration (FDA) for human use
due to hazardous side effect such as hypotension, bradycardia, respiratory depression and coma.
This is a rare case report of a 64-year-old farmer who accidentally injected himself with Xylazine
which was supposed to be given to a fractious cow. He developed altered conscious level, hypotension, bradycardia and respiratory failure requiring mechanical ventilation. Fortunately, he
recovered and was discharged home after three days. This occurred due to improper handling of
Xylazine without standard operating procedures. Xylazine is regulated for animal use only. Therefore, effects of Xylazine toxicity in human must be emphasized for awareness on proper handling as well as for right management of its poisoning incident in future.

Matched MeSH terms: Analgesics
Fulltext Pharmacogenomics biomarkers for personalized methadone maintenance treatment: The mechanism and its potential use

Ramli FF

Bosn J Basic Med Sci, 2021 Apr 01;21(2):145-154.
PMID: 32841585 DOI: 10.17305/bjbms.2020.4897

Methadone has a wide pharmacokinetic interindividual variability, resulting in unpredicted treatment response. Pharmacogenomic biomarkers seem promising for personalized methadone maintenance treatment. The evidence supports the use of ABCB1 single-nucleotide polymorphism (SNP) 1236C>T with genotypes C/T or C/C (Jewish) and haplotypes AGCTT carrier, AGCGC heterozygote, or non-carrier (Caucasian), which have a predicted lower methadone dose requirement. In contrast, ABCB1 SNP 1236C>T with genotype T/T (Jewish); haplotypes AGCGC homozygote, AGCTT non-carrier (Caucasian), and ABCB1 3435C>T variant carrier; and haplotypes CGT, TTC, and TGT (Han Chinese) have a predicted higher methadone dose. For methadone plasma levels, ABCB1 diplotype non-CGC/TTT (Malay) predicted lower, and diplotype CGC/TTT (Malay), 3435C>T allelic carrier, haplotypes (CGT, TTC, TGT) (Han Chinese) predicted higher methadone levels. In terms of metabolism biomarkers, a lower methadone requirement was related to carriers of CYP2B6 genotypes *4(G/G) and *9(T/T) among Jewish patients, CYP2B6*9 genotype (T/T) and haplotypes (TA/TG); and CYP2C19 (*2/*2,*2/*3, and *3/*3; Han Chinese). Higher methadone dose was observed in CYP2C19*1 allelic carriers (Han Chinese) and CYP2D6 ultrarapid metabolizer (Caucasian). Lower methadone levels were reported in CYP2B6 SNPs, haplotypes TTT, and AGATAA (Han Chinese), CYP2C19 genotype *1/*1 (Han Chinese), allelic carrier *1xN (Caucasian), and CYP3A4 genotype *1/*1 (Caucasian). Carriers of CYP2B6 genotype *6/*6 (Caucasian), CYP2B6 haplotypes ATGCAG and ATGCTG (Han Chinese), and CYP3A4 genotype *1/*1B (Caucasian) had predicted higher methadone plasma levels. Specific pharmacokinetics biomarkers have potential uses for personalized methadone treatment in specific populations.

Matched MeSH terms: Analgesics, Opioid/administration & dosage; Analgesics, Opioid/pharmacokinetics*
Fulltext Alternative pain management via endocannabinoids in the time of the opioid epidemic: Peripheral neuromodulation and pharmacological interventions

Lee MT, Mackie K, Chiou LC

Br J Pharmacol, 2023 Apr;180(7):894-909.
PMID: 34877650 DOI: 10.1111/bph.15771

The use of opioids in pain management is hampered by the emergence of analgesic tolerance, which leads to increased dosing and side effects, both of which have contributed to the opioid epidemic. One promising potential approach to limit opioid analgesic tolerance is activating the endocannabinoid system in the CNS, via activation of CB1 receptors in the descending pain inhibitory pathway. In this review, we first discuss preclinical and clinical evidence revealing the potential of pharmacological activation of CB1 receptors in modulating opioid tolerance, including activation by phytocannabinoids, synthetic CB1 receptor agonists, endocannabinoid degradation enzyme inhibitors, and recently discovered positive allosteric modulators of CB1 receptors. On the other hand, as non-pharmacological pain relief is advocated by the US-NIH to combat the opioid epidemic, we also discuss contributions of peripheral neuromodulation, involving the electrostimulation of peripheral nerves, in addressing chronic pain and opioid tolerance. The involvement of supraspinal endocannabinoid systems in peripheral neuromodulation-induced analgesia is also discussed. LINKED ARTICLES: This article is part of a themed issue on Advances in Opioid Pharmacology at the Time of the Opioid Epidemic. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v180.7/issuetoc.

Matched MeSH terms: Analgesics/pharmacology
Fulltext Comparative efficacy of exercise therapy and oral non-steroidal anti-inflammatory drugs and paracetamol for knee or hip osteoarthritis: a network meta-analysis of randomised controlled trials

Weng Q, Goh SL, Wu J, Persson MSM, Wei J, Sarmanova A, et al.

Br J Sports Med, 2023 Aug;57(15):990-996.
PMID: 36593092 DOI: 10.1136/bjsports-2022-105898

OBJECTIVE: Clinical guidelines recommend exercise as a core treatment for knee or hip osteoarthritis (OA). However, how its analgesic effect compares to analgesics, for example, oral non-steroidal anti-inflammatory drugs (NSAIDs) and paracetamol-the most commonly used analgesics for OA, remains unknown.
DESIGN: Network meta-analysis.
DATA SOURCES: PubMed, Embase, Scopus, Cochrane Library and Web of Science from database inception to January 2022.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised controlled trials (RCTs) comparing exercise therapy with oral NSAIDs and paracetamol directly or indirectly in knee or hip OA.
RESULTS: A total of n=152 RCTs (17 431 participants) were included. For pain relief, there was no difference between exercise and oral NSAIDs and paracetamol at or nearest to 4 (standardised mean difference (SMD)=-0.12, 95% credibility interval (CrI) -1.74 to 1.50; n=47 RCTs), 8 (SMD=0.22, 95% CrI -0.05 to 0.49; n=2 RCTs) and 24 weeks (SMD=0.17, 95% CrI -0.77 to 1.12; n=9 RCTs). Similarly, there was no difference between exercise and oral NSAIDs and paracetamol in functional improvement at or nearest to 4 (SMD=0.09, 95% CrI -1.69 to 1.85; n=40 RCTs), 8 (SMD=0.06, 95% CrI -0.20 to 0.33; n=2 RCTs) and 24 weeks (SMD=0.05, 95% CrI -1.15 to 1.24; n=9 RCTs).
CONCLUSIONS: Exercise has similar effects on pain and function to that of oral NSAIDs and paracetamol. Given its excellent safety profile, exercise should be given more prominence in clinical care, especially in older people with comorbidity or at higher risk of adverse events related to NSAIDs and paracetamol.CRD42019135166.

Matched MeSH terms: Analgesics/therapeutic use
Antinociceptive activity of a synthetic oxopyrrolidine-based compound, ASH21374, and determination of its possible mechanisms

Zakaria ZA, Sani MH, Mohammat MF, Mansor NS, Shaameri Z, Kek TL, et al.

Can J Physiol Pharmacol, 2013 Dec;91(12):1143-53.
PMID: 24289087 DOI: 10.1139/cjpp-2013-0099

This study was carried out to determine the antinociceptive activity of a novel synthetic oxopyrrolidine-based compound, (2R,3R,4S)-ethyl 4-hydroxy-1,2-dimethyl-5-oxopyrrolidine-3-carboxylate (ASH21374), and to elucidate the involvement of the opioid, vanilloid, glutamate, and nitric oxide - cyclic guanosine monophosphate (NO/cGMP) systems in modulating the observed antinociception. ASH21374, in the doses of 2, 10, and 100 mg/kg body mass, was administered orally to mice 60 mins prior to exposure to various antinociceptive assays. From the results obtained, ASH21374 exhibited significant (P < 0.05) antinociceptive activity in the abdominal constriction, hot-plate, and formalin tests that was comparable with 100 mg/kg acetylsalicylic acid or 5 mg/kg morphine, respectively. ASH21374 also attenuated capsaicin- and glutamate-induced paw licking. Pre-treatment with 5 mg/kg naloxone significantly (P < 0.05) inhibited the activity in all assays, while pretreatment with 10 mg/kg β-funaltraxamine, 1 mg/kg naltrindole, or 1 mg/kg nor-binaltorphimine significantly (P < 0.05) reversed the activity in the abdominal constriction test. l-Arginine, N(G)-nitro-l-arginine methyl esters (l-NAME), methylene blue, and their combinations, failed to inhibit the ASH21374 antinociceptive activity. In conclusion, ASH21374 demonstrated antinociceptive activities on the peripheral and central nervous systems, mediated through the activation of opioid receptors, inhibition of the glutamatergic system, and attenuation of vanilloid-mediated nociceptive transmission. Further studies have been planned to determine the pharmacological potential of ASH21374.

Matched MeSH terms: Analgesics/pharmacology*; Analgesics, Opioid/metabolism
Antinociceptive, anti-inflammatory and antipyretic properties of Melastoma malabathricum leaves aqueous extract in experimental animals

Zakaria ZA, Raden Mohd Nor RN, Hanan Kumar G, Abdul Ghani ZD, Sulaiman MR, Rathna Devi G, et al.

Can J Physiol Pharmacol, 2006 Dec;84(12):1291-9.
PMID: 17487238

The present study was carried out to establish the antinociceptive, anti-inflammatory, and antipyretic properties of the aqueous extract of Melastoma malabathricum leaves in experimental animals. The antinociceptive activity was measured using abdominal constriction, hot-plate, and formalin tests, whereas the anti-inflammatory and antipyretic activities were measured using carrageenan-induced paw edema and brewer's yeast-induced pyrexia tests, respectively. The extract, which was obtained after soaking the air-dried leaves in distilled water for 72 h and then preparing in concentrations of 10%, 50%, and 100% (v/v), was administered subcutaneously 30 min prior to subjection to the above mentioned assays. At all concentrations tested, the extract was found to exhibit significant (P < 0.05) antinociceptive, anti-inflammatory, and antipyretic activities in a concentration-independent manner. Our findings that the aqueous extract of M. malabathricum possesses antinociceptive, anti-inflammatory, and antipyretic activities supports previous claims on its traditional uses to treat various ailments.

Matched MeSH terms: Analgesics/pharmacology*; Analgesics/therapeutic use; Analgesics/chemistry; Analgesics, Non-Narcotic/pharmacology*; Analgesics, Non-Narcotic/therapeutic use; Analgesics, Non-Narcotic/chemistry
Effect of various antagonists on the Channa striatus fillet extract antinociception in mice

Zakaria ZA, Sulaiman MR, Mat Jais AM, Somchit MN

Can J Physiol Pharmacol, 2005 Jul;83(7):635-42.
PMID: 16091789

The effects of an aqueous supernatant of haruan (ASH) (Channa striatus) fillet extract on various antinociception receptor system activities were examined using a mouse abdominal-constriction model. Mice that were pretreated with distilled water, s.c., followed 10 min later by administration of 25%, 50%, and 100% concentration ASH, s.c., produced a significant concentration-dependent antinociceptive activity (p < 0.001). Pretreatment with naloxone (0.3, 1.0, and 3.0 mg/kg body mass), 10 min before ASH administration, failed to block the extract antinociception. Pretreatment of the 100% concentration ASH with mecamylamine (5 mg/kg), pindolol (10 mg/kg), and haloperidol (1 mg/kg) also did not cause any significant change in its antinociception. However, pretreatment with atropine (5 mg/kg), bicuculline (10 mg/kg), phenoxybenzamine (10 mg/kg), and methysergide (5 mg/kg) were found to reverse ASH antinociception. Based on the above findings, the ASH is suggested to contain different types of bioactive compounds that act synergistically on muscarinic, GABAA, alpha-adrenergic, and serotonergic receptor systems to produce the observed antinociception.

Matched MeSH terms: Analgesics*
Sunitinib DDI with paracetamol, diclofenac, mefenamic acid and ibuprofen shows sex-divergent effects on the tissue uptake and distribution pattern of sunitinib in mice

Tan SY, Wong MM, Tiew AL, Choo YW, Lim SH, Ooi IH, et al.

Cancer Chemother Pharmacol, 2016 10;78(4):709-18.
PMID: 27495788 DOI: 10.1007/s00280-016-3120-9

PURPOSE: Pharmacokinetic interaction of sunitinib with diclofenac, paracetamol, mefenamic acid and ibuprofen was evaluated due to their P450 mediated metabolism and OATP1B1, OATP1B3, ABCB1, ABCG2 transporters overlapping features.
METHODS: Male and female mice were administered 6 sunitinib doses (60 mg/kg) PO every 12 h and 30 min before the last dose were administered vehicle (control groups), 250 mg/kg paracetamol, 30 mg/kg diclofenac, 50 mg/kg mefenamic acid or 30 mg/kg ibuprofen (study groups), euthanized 6 h post last administration and sunitinib plasma, liver, kidney, brain concentrations analyzed.
RESULTS: Ibuprofen halved sunitinib plasma concentration in female mice (p

Matched MeSH terms: Analgesics, Non-Narcotic/pharmacology*
Chemistry and pharmacology of analgesic indole alkaloids from the rubiaceous plant, Mitragyna speciosa

Takayama H

Chem Pharm Bull (Tokyo), 2004 Aug;52(8):916-28.
PMID: 15304982

The leaves of a tropical plant, Mitragyna speciosa KORTH (Rubiaceae), have been traditionally used as a substitute for opium. Phytochemical studies of the constituents of the plant growing in Thailand and Malaysia have led to the isolation of several 9-methoxy-Corynanthe-type monoterpenoid indole alkaloids, including new natural products. The structures of the new compounds were elucidated by spectroscopic and/or synthetic methods. The potent opioid agonistic activities of mitragynine, the major constituent of this plant, and its analogues were found in in vitro and in vivo experiments and the mechanisms underlying the analgesic activity were clarified. The essential structural features of mitragynines, which differ from those of morphine and are responsible for the analgesic activity, were elucidated by pharmacological evaluation of the natural and synthetic derivatives. Among the mitragynine derivatives, 7-hydroxymitragynine, a minor constituent of M. speciosa, was found to exhibit potent antinociceptive activity in mice.

Matched MeSH terms: Analgesics, Opioid/pharmacology; Analgesics, Opioid/chemistry*
Amino acid and fatty acid composition of an aqueous extract of Channa striatus (Haruan) that exhibits antinociceptive activity

Zakaria ZA, Mat Jais AM, Goh YM, Sulaiman MR, Somchit MN

Clin Exp Pharmacol Physiol, 2007 Mar;34(3):198-204.
PMID: 17250639

1. The present study was performed in order to determine the amino acid and fatty acid composition of an aqueous extract of the freshwater fish Channa striatus, obtained by soaking (1:2, w/v) fresh fillets overnight in a chloroform:methanol (2:1, v/v) solvent, to elucidate the mechanism responsible for its antinociceptive activity and to clarify the relationship between the presence of the amino and fatty acids and the expected activity. 2. The aqueous extract was found to contain all amino acids with the major amino acids glycine, alanine, lysine, aspartic acid and proline making up 35.77 +/- 0.58, 10.19 +/- 1.27, 9.44 +/- 0.56, 8.53 +/- 1.15 and 6.86 +/- 0.78% of the total protein, respectively. 3. In addition, the aqueous extract was found to have a high palmitic acid (C16:0) content, which contributed approximately 35.93 +/- 0.63% to total fatty acids. The other major fatty acids in the aqueous extract were oleic acid (C18:1), stearic acid (C18:0), linoleic acid (C18:2) and arachidonic acid (C20:4), contributing 22.96 +/- 0.40, 15.31 +/- 0.33, 11.45 +/- 0.31 and 7.44 +/- 0.83% of total fatty acids, respectively. 4. Furthermore, the aqueous extract was demonstrated to possess concentration-dependent antinociceptive activity, as expected, when assessed using the abdominal constriction test in mice. 5. It is concluded that the aqueous extract of C. striatus contains all the important amino acids, but only some of the important fatty acids, which are suggested to play a key role in the observed antinociceptive activity of the extract, as well as in the traditionally claimed wound healing properties of the extract.

Matched MeSH terms: Analgesics/pharmacology*

Filters

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links