Involvement of imidazoline and opioid receptors in the enhancement of clonidine-induced analgesia by sulfisoxazole

2010 ◽  
Vol 88 (5) ◽  
pp. 541-552 ◽  
Author(s):  
Mustufa Boxwalla ◽  
George Matwyshyn ◽  
Bhagya L. Puppala ◽  
Shridhar V. Andurkar ◽  
Anil Gulati
Keyword(s):  
Receptor Antagonist ◽  
Opioid Receptors ◽  
Analgesic Effect ◽  
Adrenergic Receptor ◽  
Area Under The Curve ◽  
Tail Flick ◽  
Imidazoline Receptors ◽  
Adrenergic Agonist ◽  
Tail Flick Latency ◽  
Dose Dependent

Clonidine, an α2-adrenergic agonist, has been demonstrated to produce significant analgesia and potentiate morphine analgesia. Endothelin (ETA) receptor antagonists have also been found to potentiate the antinociceptive response to morphine. Clonidine and ET have been reported to have cardiovascular interactions involving the sympathetic nervous system, but it is not known whether ETA receptor antagonist affects clonidine analgesia. This study examined the influence of sulfisoxazole (ETA receptor antagonist) on clonidine analgesia. Male Swiss Webster mice were used to determine antinociceptive response of drugs by measuring tail-flick latency. The effect of clonidine (0.3, 1.0, and 3.0 mg/kg, i.p.) alone or in combination with sulfisoxazole (25, 75, and 225 mg/kg, p.o.) on analgesia and body temperature was determined. Clonidine produced a dose-dependent analgesia and hypothermia. Sulfisoxazole (25, 75, and 225 mg/kg), when administered with clonidine (0.3 mg/kg), significantly potentiated (31% increase in area under the curve (AUC)) the analgesic effect of clonidine. Yohimbine (α2-adrenergic receptor antagonist) did not affect analgesic effect of clonidine plus sulfisoxazole. Idazoxan (I1-imidazoline and α2-adrenergic receptor antagonist) reduced (47% decrease in AUC) the analgesic effect of clonidine plus sulfisoxazole. Treatment with naloxone reduced (46% decrease in AUC) the analgesic effect of clonidine plus sulfisoxazole. The effect of another ETA receptor antagonist, BMS-182874 (2, 10, and 50 µg, i.c.v.) was studied, and it was found that the dose of 10 µg significantly potentiated (26% increase in AUC) the analgesic effect of clonidine. These results indicate that sulfisoxazole, an ETA receptor antagonist, potentiates the analgesic effect of clonidine, which could be mediated through I1-imidazoline receptors and opioid receptors.

Semi-synthesis of Novel Buprenorphine Derivatives and their Anti-nociceptive Properties and Dependency Potential

2021 ◽  
Author(s):  
Zahra Hasanpour ◽  
Peyman Salehi ◽  
Lennart Bunch ◽  
Mona Khoramjouy ◽  
Morteza Bararjanian ◽  
...  
Keyword(s):  
Opioid Receptors ◽  
Analgesic Effect ◽  
Preference Test ◽  
Biological Properties ◽  
Place Preference ◽  
Tail Flick ◽  
Tail Flick Test ◽  
Active Compounds ◽  
Methyl Group ◽  
Analgesic Activities

Abstract: Novel 1,2,3-triazole-tethered N-norbuprenorphine derivatives with an OMe or OH group at the C3 position were synthesized alongside with evaluation of their analgesic properties. The analgesic activities of the resulting library were investigated via tail flick test in mice. Our results indicated that 10b and 10e were as effective as the starting compounds 8 and 9 with ED50 equal to 16.59 and 19.44 mg/kg, respectively. To investigate the effect of a methyl group at C3 on biological properties, the most active compounds were O-demethylated and their anti-nociceptive effects were assessed. The new O-demethylated derivatives (11b and 11e) showed better analgesic properties than the parent compounds with ED50 of 14.73 and 15.80 mg/kg, respectively. Naloxone prevented the analgesic effect of the synthesized compounds, indicating that the opioid receptors are highly involved in the anti-nociceptive effects of these. The potential dependency effects of the most potent derivatives were studied by condition place preference test in mice and compared to morphine and buprenorphine. Interestingly, 10b, 10e, 11b, and 11e did not show any dependency effect, similar to buprenorphine.

scholarly journals Mechanisms of L-Triiodothyronine-Induced Inhibition of Synaptosomal Na+-K+-ATPase Activity in Young Adult Rat Brain Cerebral Cortex

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Pradip K. Sarkar ◽  
Avijit Biswas ◽  
Arun K. Ray ◽  
Joseph V. Martin
Keyword(s):  
Cerebral Cortex ◽  
Atpase Activity ◽  
Adrenergic Receptor ◽  
Receptor Activation ◽  
Mammalian Brain ◽  
Neuronal Membrane ◽  
Dependent Manner ◽  
Adrenergic Agonist ◽  
Adult Rat ◽  
Dose Dependent

The role of thyroid hormones (TH) in the normal functioning of adult mammalian brain is unclear. Our studies have identified synaptosomal Na+-K+-ATPase as a TH-responsive physiological parameter in adult rat cerebral cortex. L-triiodothyronine (T3) and L-thyroxine (T4) both inhibited Na+-K+-ATPase activity (but not Mg2+-ATPase activity) in similar dose-dependent fashions, while other metabolites of TH were less effective. Although both T3and theβ-adrenergic agonist isoproterenol inhibited Na+-K+-ATPase activity in cerebrocortical synaptosomes in similar ways, theβ-adrenergic receptor blocker propranolol did not counteract the effect of T3. Instead, propranolol further inhibited Na+-K+-ATPase activity in a dose-dependent manner, suggesting that the effect of T3on synaptosomal Na+-K+-ATPase activity was independent ofβ-adrenergic receptor activation. The effect of T3on synaptosomal Na+-K+-ATPase activity was inhibited by theα2-adrenergic agonist clonidine and by glutamate. Notably, both clonidine and glutamate activateGi-proteins of the membrane second messenger system, suggesting a potential mechanism for the inhibition of the effects of TH. In this paper, we provide support for a nongenomic mechanism of action of TH in a neuronal membrane-related energy-linked process for signal transduction in the adult condition.

scholarly journals EFFECTS OF NEW PIPERIDINE DERIVATIVES WITH SUBSTITUTIONS IN THE 1ST AND 4TH POSITIONS IN NALOXONE SENSITIVE ANALGESY

2021 ◽  
Vol 19 (5) ◽  
pp. 501-505
Author(s):  
A. A. Vasilyuk ◽  
◽  
V. I. Kozlovsky ◽  
G. S. Akhmetova ◽  
V. K. Yu ◽  
...  
Keyword(s):  
Pain Relief ◽  
Receptor Antagonist ◽  
Opioid Receptor ◽  
Opioid Receptors ◽  
Analgesic Effect ◽  
Chemical Stimulation ◽  
Analgesic Action ◽  
Preliminary Administration ◽  
Chemical Irritation

Background. Despite the wide arsenal of painkillers, pain relief is an urgent interdisciplinary problem that requires a search for new solutions. Purpose of the study. To establish the role of opioid receptors in the mechanism of the analgesic action of the piperidine derivatives AGV-22 and AGV-23. Material and methods. The studies were carried out on 96 white mice of both sexes weighing 30-40 g. The analgesic effect of the compounds was tested on models of thermal and chemical irritation with preliminary administration of the opioid receptor antagonist naloxone. Results. The pain reactions of mice with models of thermal and chemical stimulation in the AGV-22 / AGV-23 + naloxone and AGV-22 / AGV-23 groups were comparable. Conclusions. The mechanism of the analgesic action of the piperidine derivatives AGV-22 and AGV-23 is not associated with the activation of opioid receptors.

5-HT1A Receptors Mediate Analgesia Induced by Emulsified Sevoflurane in Thermal Nociception but Have Little Effect on Chemical Nociception

Pharmacology ◽  
2017 ◽  
Vol 100 (1-2) ◽  
pp. 25-30
Author(s):  
Chen Yan ◽  
Dai Ti-jun ◽  
Li Xin ◽  
Cao Gao ◽  
Jiang Shen ◽  
...  
Keyword(s):  
Analgesic Effect ◽  
Intraperitoneal Injection ◽  
Serotonin Receptor ◽  
Intrathecal Injection ◽  
Tail Flick ◽  
Hot Plate Test ◽  
Thermal Nociception ◽  
Tail Flick Latency ◽  
Specific Antagonist ◽  
The Relationship

Objective: The study aimed to investigate the relationship between the analgesic effect of sevoflurane and 5-serotonin receptor 1A (5-HT1A R) in the spinal cords of mice. Methods: Analgesic mouse models were established by intraperitoneal injection of emulsified sevoflurane, and the influence of p-MPPF (a specific antagonist of 5-HT1A Rs) intrathecal injection on the changes in tail-flick latency in tail-withdrawal test, pain threshold in hot-plate test (HPPT), and writhing times in acetic acid-induced writhing test were recorded. Results: Intraperitoneal injection of emulsified sevoflurane alone produced an analgesic effect (p < 0.05). p-MPPF (2, 4, and 8 μg) alone had no impact on tail-flick latency, HPPT, and writhing times in mice (p > 0.05). The 3 doses of p-MPPF reduced the tail-flick latency or HPPT. p-MPPF 8 μg can increase the writhing times (p < 0.05) in analgesic mice with sevoflurane, while p-MPPF 2 and 4 μg did not affect the writhing times. Conclusion: 5-HT1A Rs in the spinal cord may be an important target for the analgesic effect of sevoflurane on the thermal nociception, but it has little relation to the anti-chemical chemical nociceptive effect of sevoflurane.

Antinociceptive Interaction of Intrathecal α2-adrenergic Agonists, Tizanidine and Clonidine, with Lidocaine in Rats 

1997 ◽  
Vol 87 (2) ◽  
pp. 436-448 ◽  
Author(s):  
Tomoyuki Kawamata ◽  
Keiichi Omote ◽  
Mikito Kawamata ◽  
Hiroshi Iwasaki ◽  
Akiyoshi Namiki
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Motor Function ◽  
Antinociceptive Effect ◽  
Synergistic Interaction ◽  
Tail Flick ◽  
Adrenergic Agonist ◽  
Potency Ratio ◽  
Isobolographic Analysis ◽  
Tail Flick Latency

Background The intrathecal alpha2-adrenergic agonist, clonidine, has been shown to have considerable antinociceptive effect, although clonidine causes hypotension and bradycardia. The combination of intrathecal clonidine and local anesthetics enhances analgesic effects, whereas the combination may cause marked hypotension and motor blockade, which may limit the clinical application of the combination. Tizanidine, another alpha2-adrenergic agonist, has also provided antinociception without producing pronounced hemodynamic changes. This study was designed to evaluate the antinociceptive and hemodynamic interactions of tizanidine and clonidine with lidocaine. Methods Male Sprague Dawley rats were chronically implanted with lumbar intrathecal catheters. The tail-flick test was used to assess the thermal nociceptive threshold. The ability of intrathecal tizanidine, clonidine, lidocaine, or the combinations of alpha2-adrenergic agonist and lidocaine to alter the tail-flick latency was examined. To characterize the antinociceptive interaction, the isobolographic analysis was applied. Additionally, the motor function, blood pressure and heart rate after intrathecal administration of drugs and combinations were also monitored. Results Intrathecal tizanidine, clonidine, or the combinations increased the tail-flick latency in dose- and time-dependent fashion without affecting motor function. The order potencies (dose producing a 50% of peak effect, in microg) of tizanidine and clonidine were 1.8 and 0.75, respectively. With isobolographic analysis, tizanidine with lidocaine and clonidine with lidocaine showed significantly synergistic antinociceptive interaction. Potency ratio analysis and fractional analysis also confirmed the synergistic interaction. At the doses in the combinations showing comparable antinociception, tizanidine with lidocaine, unlike clonidine with lidocaine, did not affect motor function or blood pressure. Conclusion The authors' results show that intrathecal tizanidine and clonidine synergistically interact with lidocaine so that the degree of antinociception to somatic noxious stimuli are enhanced. The antinociceptive synergistic interaction between tizanidine and lidocaine may be useful in clinical practice without affecting blood pressure, heart rate, or motor function.

scholarly journals The Analgesic Effect of Venlafaxine and Its Mechanism on Oxaliplatin-Induced Neuropathic Pain in Mice

2019 ◽  
Vol 20 (7) ◽  
pp. 1652 ◽  
Author(s):  
Daxian Li ◽  
Ji Lee ◽  
Chang Choi ◽  
Jaihwan Kim ◽  
Sun Kim ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Receptor Antagonist ◽  
Analgesic Effect ◽  
Adrenergic Receptor ◽  
Mechanical Allodynia ◽  
Intraperitoneal Administration ◽  
Cold Allodynia ◽  
Oxaliplatin Treatment ◽  
Noradrenaline Reuptake ◽  
Adrenergic Antagonist

The analgesic effect of venlafaxine (VLX), which is a selective serotonin and noradrenaline reuptake inhibitor (SNRI), has been observed on oxaliplatin-induced neuropathic pain in mice. Significant allodynia was shown after oxaliplatin treatment (6 mg/kg, i.p.); acetone and von Frey hair tests were used to assess cold and mechanical allodynia, respectively. Intraperitoneal administration of VLX at 40 and 60 mg/kg, but not 10 mg/kg, significantly alleviated these allodynia. Noradrenaline depletion by pretreatment of N-(2-Chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4, 50 mg/kg, i.p.) blocked the relieving effect of VLX (40 mg/kg, i.p.) on cold and mechanical allodynia. However, serotonin depletion by three consecutive pretreatments of para-chlorophenylalanine (PCPA, 150 mg/kg/day, i.p.) only blocked the effect of VLX on mechanical allodynia. In cold allodynia, the α2-adrenergic antagonist idazoxan (10 μg, i.t.), but not the α1-adrenergic antagonist prazosin (10 μg, i.t.), abolished VLX-induced analgesia. Furthermore, idazoxan and 5-HT3 receptor antagonist bemesetron (MDL-72222, 15 μg, i.t.), but not prazosin or mixed 5-HT1, 2 receptor antagonist methysergide (10 μg, i.t.), abolished VLX-induced analgesia in mechanical allodynia. In conclusion, 40 mg/kg of VLX treatment has a potent relieving effect against oxaliplatin-induced neuropathic pain, and α2-adrenergic receptor, and both α2-adrenergic and 5-HT3 receptors are involved in this effect of VLX on cold and mechanical allodynia, respectively.

scholarly journals Study of analgesic property of diacerein in rat

2020 ◽  
Vol 8 (12) ◽  
pp. 4316
Author(s):  
Rajlaxmi Upadhyay ◽  
Goutam Siddhartha ◽  
Manas Ranjan Upadhyay ◽  
Trupti Rekha Swain
Keyword(s):  
Pilot Study ◽  
Analgesic Activity ◽  
Analgesic Effect ◽  
Wistar Rats ◽  
Tail Flick ◽  
Distilled Water ◽  
Spinal Level ◽  
Analgesic Drugs ◽  
Analgesic Property ◽  
Tail Flick Latency

Background: Diacerein has been known as an anti-osteoarthritic agent that is usually given along with other analgesic drugs. Still there is no evidence of the analgesic effect of diacerein alone. So this pilot study was undertaken to assess the analgesic property at supra-spinal level by using the tail-flick method.Methods: Diacerein at doses of 50, 100 and 200 mg/kg was given to Albino wistar rats weighing approximately 100-200 grams along with distilled water as placebo. All drugs were given by oral routes and the analgesic effect was evaluated using analgesiometer at baseline, 15 min, 30 min, 60 min and 120 min. Analgesic activity was measured as change in tail flick latency from baseline in animals.Results: Diacerein showed significant increase in tail flick latency and showed promising analgesic activity compared to placebo starting from 15 mins till 60 mins. However the effect persisted up to one hour only and after which it started decreasing.Conclusions: Diacerein at all the three doses possess dose dependant analgesic activity that is maximally effective up to 60 minutes.

scholarly journals Expression of adrenergic receptors in mouse preimplantation embryos and ovulated oocytes

Reproduction ◽  
2007 ◽  
Vol 133 (6) ◽  
pp. 1139-1147 ◽  
Author(s):  
Štefan Čikoš ◽  
Pavol Rehák ◽  
Soňa Czikková ◽  
Jarmila Veselá ◽  
Juraj Koppel
Keyword(s):  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Cell Number ◽  
Embryo Cell ◽  
Preimplantation Embryos ◽  
Adrenergic Agonist ◽  
And Migration ◽  
Β Adrenergic Receptors ◽  
Dose Dependent ◽  
Receptor Family

Epinephrine and norepinephrine can play an important role in basic developmental processes such as embryogenesis and morphogenesis, regulating cell proliferation, differentiation and migration. We showed that β-adrenergic receptors can mediate the effects of catecholamines on preimplantation embryos in our previous work. In the present study, we designed specific oligonucleotide primers which can distinguish among all members of the α-adrenergic receptor family, and showed (using RT-PCR) that the α2C-adrenergic receptor is transcribed in ovulated oocytes, 8- to 16-cell morulae and expanded blastocysts. We did not detect the α2C-adrenoceptor transcript in 4-cell embryos. Our immunohistochemical study showed the presence of α-2C-adrenoceptor protein in ovulated oocytes, 8- to 16- cell embryos and blastocysts, but the signal in 4-cell embryos was weak, and probably represents remaining protein of maternal origin. We did not detect any other α-adrenergic receptor in preimplantation embryos and oocytes. Exposure of mouse preimplantation embryos to the α2-adrenergic agonist UK 14 304 led to significant reduction of the embryo cell number, and the effect was dose dependent. Our results suggest that epinephrine and norepinephrine could affect the embryo development in the oviduct via adrenergic receptors directly and support the opinion that maternal stress can influence the embryo even in very early pregnancy.

Central lipopolysaccharide elevates plasma IL-6 concentration by an alpha-adrenoreceptor-mediated mechanism

1997 ◽  
Vol 272 (6) ◽  
pp. R1880-R1887 ◽  
Author(s):  
B. N. Finck ◽  
R. Dantzer ◽  
K. W. Kelley ◽  
J. A. Woods ◽  
R. W. Johnson
Keyword(s):  
Receptor Antagonist ◽  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Alpha Adrenergic Receptor ◽  
Inflammatory Stimuli ◽  
Dose Dependent Fashion ◽  
Subsequent Activation ◽  
Dose Dependent ◽  
The Brain ◽  
Circulating Levels

High circulating levels of interleukin-6 (IL-6) are evident after intracerebroventricular injection of lipopolysaccharide (LPS). To investigate the pathway of centrally induced IL-6 production, in the present study we evaluated the effects of specific alpha-adrenergic receptor antagonists administered peripherally on IL-6 production and hypertriglyceridemia induced by LPS administered centrally. In the first study, adult male Wistar-Furth rats were injected intracerebroventricularly with LPS. Centrally injected LPS increased plasma IL-6 and triglycerides (TG) in a dose-dependent fashion. To determine if LPS increased plasma IL-6 and TG through an alpha-adrenoreceptor mechanism, rats were pretreated intraperitoneally with either vehicle, phentolamine (alpha 1- and alpha 2-receptor antagonist), prazosin (alpha 1-receptor antagonist), or yohimbine (alpha 2-receptor antagonist). Thirty minutes later, rats were injected intracerebroventricularly with LPS. Whereas prazosin and yohimbine attenuated the increases in plasma IL-6 caused by LPS, phentolamine completely blocked the peripheral effects of central LPS. These data suggest that increased sympathetic activity and subsequent activation of alpha 1- and alpha 2-adrenergic receptors are important for controlling peripheral metabolic and endocrine systems when inflammatory stimuli are present in the brain.

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