scholarly journals Pharmacokinetics and Pharmacodynamics of diclofenac in the presence and absence of glibenclamide in the rat

2016 ◽  
Vol 11 (3) ◽  
pp. 68 ◽  
Author(s):  
María R León-Reyes ◽  
Gilberto Castañeda-Hernández ◽  
Mario I Ortiz
Keyword(s):  
Formalin Test ◽  
Antinociceptive Effect ◽  
Dorsal Surface ◽  
Pharmacokinetic Interaction ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Female Wistar Rats ◽  
Inflammatory Drugs ◽  
The Right ◽  
Dose Dependent ◽  
Analgesic Response

PURPOSE. There are evidences that glibenclamide, a sulfonylurea antidiabetic agent, reduces the analgesic action of non-steroidal anti-inflammatory drugs (NSAIDs), opioids and neuromodulators in animal models. The purpose of this work was to examine in the rat if such interaction involves pharmacokinetic mechanisms or is solely limited to the pharmacodynamic level. METHODS. All studies were carried out in female Wistar rats. Analgesia was assessed using the formalin test. Fifty microliters of diluted formalin was injected subcutaneously into the dorsal surface of the right hind paw. Nociceptive behavior was quantified as the number of flinches of the injected paw during 60 min after injection and a reduction in formalin-induced flinching was interpreted as an analgesic response. Rats were treated with oral diclofenac (3-18 mg/kg) in presence and the absence of oral glibenclamide (1-30 mg/kg). To evaluate the possibility of a pharmacokinetic interaction, the oral bioavailability of diclofenac (18 mg/kg) was studied in presence and the absence of glibenclamide (10 mg/kg). RESULTS. Oral administration of diclofenac produced a dose-dependent antinociceptive effect in the formalin test. Coadministration of glibenclamide significantly reduced diclofenac-induced antinociception. Notwithstanding, the interaction does no appear to involve pharmacokinetic mechanisms, as oral glibenclamide failed to produce any significant alteration in oral diclofenac bioavailability. CONCLUSION. Concomitant systemic administration of glibenclamide and diclofenac results in a reduction of the analgesic effect of the NSAID in the formalin test in the rat. This interaction, however, appears due solely to a pharmacodynamic mechanisms as diclofenac pharmacokinetics are not altered.

Role of the NO-cGMP-K+ channels pathway in the peripheral antinociception induced by α-bisabolol

2021 ◽  
Author(s):  
Mario I Ortiz ◽  
Raquel Cariño-Cortés ◽  
Victor Manuel Muñoz Pérez ◽  
Andres Salas Casas ◽  
Gilberto Castañeda-Hernández
Keyword(s):  
Opioid Receptors ◽  
Formalin Test ◽  
Antinociceptive Effect ◽  
Dorsal Surface ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
K Channel ◽  
Formalin Injection ◽  
K Channels ◽  
The Right

The aim of this study was to examine if the peripheral antinociception of α-bisabolol involve the participation of nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) synthesis followed by K+ channel opening in the formalin test. Wistar rats were injected in the dorsal surface of the right hind paw with formalin (1%). Rats received a subcutaneous injection into the dorsal surface of the paw of vehicles or increasing doses of α-bisabolol (100-300 µg/paw). To determine whether the peripheral antinociception induced by α-bisabolol was mediated by either the opioid receptors or the NO-cGMP-K+ channels pathway, the effect of pretreatment (10 min before formalin injection) with the appropriate vehicles, naloxone, naltrexone, L-NAME, ODQ, glibenclamide, glipizide, apamin, charybdotoxin, tetraethylammonium or 4-aminopyridine on the antinociceptive effects induced by local peripheral α-bisabolol (300 µg/paw) were assessed. α-bisabolol produced antinociception during both phases of the formalin test. α-bisabolol antinociception was blocked by L-NAME, ODQ, and all the K+ channels blockers. The peripheral antinociceptive effect produced by α-bisabolol was not blocked by the opioid receptor inhibitors. α-bisabolol was able to active the NO-cGMP-K+ channels pathway in order to produce its antinoceptive effect. The participation of opioid receptors in the peripheral local antinociception induced by α-bisabolol is excluded.

scholarly journals Pharmacokinetic of Diclofenac in the Presence and Absence of Glibenclamide in the Rat

2009 ◽  
Vol 12 (3) ◽  
pp. 280 ◽  
Author(s):  
María R. León-Reyes ◽  
Gilberto Castañeda-Hernández ◽  
Mario I Ortiz
Keyword(s):  
Oral Administration ◽  
Formalin Test ◽  
Antinociceptive Effect ◽  
Dorsal Surface ◽  
Pharmacokinetic Interaction ◽  
Pharmacokinetic Profile ◽  
Pharmacokinetic Parameters ◽  
Formalin Injection ◽  
Pharmacodynamic Interaction ◽  
Chromatography Method

ABSTRACT - PURPOSE. There is evidence that the sulfonylurea antidiabetic agent glibenclamide reduces the analgesic action of non-steroidal anti-inflammatory drugs (NSAIDs), opioids and neuromodulators in animal models. Therefore, in view of the vast clinical uses and interactions of NSAIDs with commonly used therapeutic agents, the interaction of the NSAID diclofenac and glibenclamide was investigated about pharmacokinetic profile and antinociceptive effect in rats. METHODS. Antinociception was assessed using the formalin test. Fifty microliters of diluted formalin was injected s.c. into the dorsal surface of the right hind paw. Nociceptive behavior was quantified as the number of flinches of the injected paw during 60 min after injection. Rats were treated with oral administration of vehicle or increasing doses of diclofenac (3-18 mg/kg) before formalin injection. To determine the pharmacodynamic interaction between diclofenac and glibenclamide, the effect of oral administration of glibenclamide (1-30 mg/kg) on the antinociceptive effect induced by diclofenac (18 mg/kg, p.o.) was assessed. To evaluate the pharmacokinetic interaction between diclofenac and glibenclamide, the effect of glibenclamide (10 mg/kg, p.o.) on the pharmacokinetic of diclofenac (18 mg/kg, p.o.) was studied in the rat. Blood samples were taken over 8 h and analyzed using a validated high-performance liquid chromatography method to generate the pharmacokinetic profile of diclofenac. Pharmacokinetic parameters were estimated using noncompartmental analysis. RESULTS. Systemic administration of diclofenac produced a dose-dependent antinociceptive effect in the formalin test. Systemic treatment with glibenclamide prevented diclofenac-induced antinociception. In pharmacokinetic interaction study, no significant (P>0.05) change in diclofenac concentration-time profiles in the presence of glibenclamide was detected. CONCLUSION. The experimental findings suggest that systemic glibenclamide is able to block the diclofenac-induced antinociception in the rat formalin test. Besides, this antagonism was not produced by diminution in the bioavailability of diclofenac. Likewise, the validated assay had sufficient accuracy and precision for pharmacokinetic determination of diclofenac in the rat.

Peripheral Antinociceptive Action of Morphine and the Synergistic Interaction with Lamotrigine

2002 ◽  
Vol 96 (4) ◽  
pp. 921-925 ◽  
Author(s):  
Carlos F. Argüelles ◽  
Jorge E. Torres-López ◽  
Vinicio Granados-Soto
Keyword(s):  
Formalin Test ◽  
Glutamate Release ◽  
Antinociceptive Effect ◽  
Na Channels ◽  
Afferent Neurons ◽  
Functional Interaction ◽  
Functional Interactions ◽  
Antinociceptive Effects ◽  
Voltage Dependent ◽  
Female Wistar Rats

Background Lamotrigine inhibits glutamate release through the preferential blockade of voltage-dependent Na+ channels. In contrast, morphine reduces release of excitatory amino acids through the activation of opioid receptors and also inhibits tetrodotoxin-resistant Na+ channels on peripheral afferent neurons. The current study was designed to investigate the antinociceptive effects of locally administered morphine and lamotrigine. The interaction between morphine and lamotrigine at the periphery was also examined. Methods Morphine, lamotrigine, or a combination of morphine and lamotrigine was administered locally to female Wistar rats, and the antinociceptive effect was determined in the formalin test. Isobolographic analyses were used to define the nature of the functional interactions between morphine and lamotrigine. Results Peripheral administration of either morphine or lamotrigine produced a dose-related antinociceptive effect. Isobolographic analyses revealed that peripheral morphine and lamotrigine interacted synergistically in the formalin test. Conclusions The study shows a functional interaction between lamotrigine and morphine at the peripheral level.

scholarly journals Non-steroidal Anti-inflammatory Drugs in Tonic, Phasic and Inflammatory Mouse Models

Drug Research ◽  
2019 ◽  
Vol 69 (10) ◽  
pp. 572-578 ◽  
Author(s):  
Hugo F. Miranda ◽  
Viviana Noriega ◽  
Fernando Sierralta ◽  
Paula Poblete ◽  
Nicolas Aranda ◽  
...  
Keyword(s):  
Phase Ii ◽  
Antinociceptive Effect ◽  
Tail Flick ◽  
Tail Flick Test ◽  
Principal Mechanism ◽  
Writhing Test ◽  
A Value ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
Dose Dependent

AbstractThe principal mechanism of action of non-steroidal anti-inflammatory drugs (NSAIDs) is the inhibition of ciclooxigenases. In this study was evaluated if NSAIDs could induce antinociceptive differences according to the type of murine pain model. Male mice were injected intraperitoneally with meloxicam, diclofenac, piroxicam, metamizol, ibuprofen, naproxen and paracetamol in the writhing, tail flick and formalin orofacial tests and dose-response were analyzed to obtain the ED50 of each drugs. Administration of NSAIDs produced in a dose-dependent antinociception with different potency in the tests. The relative potency of NSAIDs among the tests shows a value of 5.53 in the orofacial formalin test in phase I and 6.34 in phase II between meloxicam and paracetamol; of 7.60 in the writhing test between meloxicam and paracetamol and of 8.46 in the tail flick test between ibuprofen and paracetamol. If the comparison is made for each NSAID in the different tests, the minimum value was 0.01 for between writhing and phase II of the orofacial formalin. Meanwhile, the highest power ratio was 11.71 for diclofenac between writhing and tail flick tests. In conclusion, the results suggests that intraperitoneal NSAIDs administration induce antinociceptive activity depending on the type of pain. The results support that NSAIDs administration, induce a wide variety of antinociceptive effect, depending on the type of pain. This suggest the participation of different mechanisms of action that can be added to the simple inhibition of COXs controlled by NSAIDs.

Orofacial Analgesic-Like Activity of Carvacrol in Rodents

2012 ◽  
Vol 67 (9-10) ◽  
pp. 481-485 ◽  
Author(s):  
Adriana G. Guimarães ◽  
Francilene V. Silva ◽  
Maria A. Xavier ◽  
Márcio R. V. Santos ◽  
Rita C. M. Oliveira ◽  
...  
Keyword(s):  
Formalin Test ◽  
Orofacial Pain ◽  
Antinociceptive Effect ◽  
Distilled Water ◽  
Depressant Effect ◽  
Upper Lip ◽  
Cns Depressant ◽  
The Central Nervous System ◽  
The Right ◽  
Orofacial Nociception

Carvacrol (CARV) is a phenolic monoterpene present in the essential oil of several aromatic spices. The purpose of the present study was to evaluate the antinociceptive effect of CARV on formalin-, capsaicin-, and glutamate-induced orofacial nociception in mice. Male mice were pretreated with CARV [25, 50, and 100 mg/kg body weight (BW), intraperitoneal (i.p.)], morphine (5 mg/kg BW, i.p.), or vehicle (distilled water + one drop of 0.3% cremophor in distilled water), before formalin (20 μl, 2%), capsaicin (20 μl, 2.5 μg), or glutamate (40 μl, 25 μM) was injected into the right upper lip. Our results revealed that i.p. pretreatment with CARV was effective in reducing the nociceptive face-rubbing behaviour in both phases of the formalin test and also produced a signifi cant antinociceptive effect at all doses in the capsaicin and glutamate tests. Further, we showed that the action of CARV on the central nervous system (CNS) did not affect these results, since this compound did not exert a significant CNS-depressant effect, as shown by the pentobarbital-induced hypnosis. Our results suggest that CARV might represent an important tool for the treatment of orofacial pain

Participation of the opioid receptor – nitric oxide – cGMP – K+ channel pathway in the peripheral antinociceptive effect of nalbuphine and buprenorphine in rats

2020 ◽  
Vol 98 (11) ◽  
pp. 753-762
Author(s):  
Mario I. Ortiz ◽  
Raquel Cariño-Cortés ◽  
Gilberto Castañeda-Hernández
Keyword(s):  
Nitric Oxide ◽  
Channel Blocker ◽  
Antinociceptive Effect ◽  
Dorsal Surface ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
K Channel ◽  
Formalin Injection ◽  
Opioid Agonist ◽  
The Right

The aim of this study was to examine if the peripheral antinociceptive effects of the opioid agonist/antagonist nalbuphine and buprenorphine involve the sequential participation of nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) synthesis followed by K+ channel opening in the formalin test. Wistar rats (180–220 g) were injected in the dorsal surface of the right hind paw with formalin (1%). Rats received a subcutaneous (s.c.) injection into the dorsal surface of the paw of vehicles or increasing doses of nalbuphine (50–200 μg/paw) or buprenorphine (1–5 μg/paw) 20 min before formalin injection into the paw. Nalbuphine antinociception was reversed by the s.c. injection into the paw of the inhibitor of NO synthesis (NG-nitro-l-arginine methyl ester (L-NAME)), by the inhibitor of guanylyl cyclase (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ)), by the Kir6.1–2, ATP-sensitive K+ channel inhibitors (glibenclamide and glipizide), by the KCa2.1–3, small conductance Ca2+-activated K+ channel blocker (apamin), by the KCa1.1, large conductance Ca2+-activated K+ channel blocker (charybdotoxin), and by the KV, voltage-dependent K+ channel inhibitors (4-aminopyridine (4-AP) and tetraethylammonium chloride (TEA)). The antinociceptive effect produced by buprenorphine was blocked by the s.c. injection of 4-AP and TEA but not by L-NAME, ODQ, glibenclamide, glipizide, apamin, or charybdotoxin. The present results provide evidence for differences in peripheral mechanisms of action between these opioid drugs.

Antinociceptive Effect of the Intrathecal Phosphodiesterase Inhibitor, Zaprinast, in a Rat Formalin Test

2005 ◽  
Vol 18 (2) ◽  
pp. 99 ◽  
Author(s):  
Burn Young Heo ◽  
Chang Mo Kim ◽  
Sung Tae Jeong ◽  
Seok Jai Kim ◽  
Jeong Il Choi ◽  
...  
Keyword(s):  
Formalin Test ◽  
Antinociceptive Effect ◽  
Phosphodiesterase Inhibitor

scholarly journals Comprehensive Review of Knee Osteoarthritis Pharmacological Treatment and the Latest Professional Societies’ Guidelines

2021 ◽  
Vol 14 (3) ◽  
pp. 205
Author(s):  
Dragan Primorac ◽  
Vilim Molnar ◽  
Vid Matišić ◽  
Damir Hudetz ◽  
Željko Jeleč ◽  
...  
Keyword(s):  
Knee Osteoarthritis ◽  
Platelet Rich Plasma ◽  
Symptom Relief ◽  
Topical Administration ◽  
Symptomatic Therapy ◽  
Therapy Options ◽  
Professional Societies ◽  
Inflammatory Drugs ◽  
The Right

Osteoarthritis is the most common musculoskeletal progressive disease, with the knee as the most commonly affected joint in the human body. While several new medications are still under research, many symptomatic therapy options, such as analgesics (opioid and non-opioid), nonsteroid anti-inflammatory drugs, symptomatic slow-acting drugs in osteoarthritis, and preparations for topical administration, are being used, with a diverse clinical response and inconsistent conclusions across various professional societies guidelines. The concept of pharmacogenomic-guided therapy, which lies on principles of the right medication for the right patient in the right dose at the right time, can significantly increase the patient’s response to symptom relief therapy in knee osteoarthritis. Corticosteroid intra-articular injections and hyaluronic acid injections provoke numerous discussions and disagreements among different guidelines, even though they are currently used in daily clinical practice. Biological options, such as platelet-rich plasma and mesenchymal stem cell injections, have shown good results in the treatment of osteoarthritis symptoms, greatly increasing the patient’s quality of life, especially when combined with other therapeutic options. Non-inclusion of the latter therapies in the guidelines, and their inconsistent stance on numerous therapy options, requires larger and well-designed studies to examine the true effects of these therapies and update the existing guidelines.

Serotonin stimulates GH secretion through a direct pituitary action: studies in hypophysectomized autografted animals and in perifused pituitaries

1986 ◽  
Vol 113 (3) ◽  
pp. 317-322 ◽  
Author(s):  
F. López ◽  
D. Gónzalez ◽  
E. Aguilar
Keyword(s):  
Plasma Volume ◽  
Direct Action ◽  
Experimental Models ◽  
Male Rats ◽  
Blood Samples ◽  
Kidney Capsule ◽  
Gh Secretion ◽  
Significant Release ◽  
The Right ◽  
Dose Dependent

Abstract. To analyze a possible direct action of serotonin (5-hydroxytryptamine) at pituitary level in GH secretion, two experimental models were used: hypophysectomized autografted rats and perifused pituitaries. Adult male rats were hypophysectomized and their own pituitaries placed under the right kidney capsule. Ten days later an intra-atrial cannula was inserted. The next day, blood samples were obtained before and every 10 min during a 2 h period after the injection of saline or 5-hydroxytryptamin (1 or 2 mg/kg iv). Plasma volume was replaced with saline. Both doses of 5-hydroxytryptamine elicit a strong release of GH, the effect being dose-dependent. In pituitaries perifused with 5-hydroxytryptamine (100 μm during 115 min or 1, 10 and 100 μm during 15 min), a significant release of GH was also observed. These results suggested that 5-hydroxytryptamine may stimulate GH secretion through a direct pituitary action.

Myiasis in Bufo regularis caused by a Tabanid Larva

Parasitology ◽  
1924 ◽  
Vol 16 (1) ◽  
pp. 111-112
Author(s):  
Edward Hindle
Keyword(s):  
Fibrous Tissue ◽  
Dorsal Surface ◽  
Body Cavity ◽  
The Body ◽  
Careful Examination ◽  
Large Female ◽  
Considerable Time ◽  
Ventral Region ◽  
Cylindrical Structure ◽  
The Right

In December, 1922, whilst dissecting a large female example of Bufo regularis, one of my students noticed a cylindrical structure extending along the ventral region of the body-cavity. A careful examination showed that this structure consisted of an elongated sac-like diverticulum of the right lung, containing an almost full-grown specimen of a dipterous larva, which could be seen through the membraneous wall of the diverticulum. The base of the latter, in addition to its point of origin from the lung, was also connected to the dorsal surface of the liver by strands of fibrous tissue, suggesting that the growth had been in existence some considerable time in order to cause such adhesions. Posteriorly, the diverticulum hung freely in the body cavity and extended to the extreme hinder end. Its dimensions were 5·5 cm. in length, by 0·5 cm. in diameter, but tapering towards each extremity.

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