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The purpose of this study is to assess the possible anti-allodynic and antihyperalgesic effect of valnoctamide, an amide derivative of valproic acid, at the doses of 40, 70 and 100 mg/kg (i.p.) in neuropathic pain model induced by chronic... more
The purpose of this study is to assess the possible anti-allodynic and antihyperalgesic effect of valnoctamide, an amide derivative of valproic acid, at the doses of 40, 70 and 100 mg/kg (i.p.) in neuropathic pain model induced by chronic constriction injury in rats, by using dynamic plantar test and plantar test (Hargreaves method), and to evaluate that the possible role of certain serotonin, noradrenergic, opioid and GABAergic receptors by pre-treatment with 1 mg/kg (i.p.) ketanserin, yohimbine, naloxone and 0.5 mg/kg (i.p.) bicuculline, respectively. 70 and 100 mg/kg valnoctamide significantly increased the mechanical and thermal thresholds decreasing with the development of neuropathy and demonstrated anti-allodynic and antihyperalgesic activity. Limited contribution of serotonin 5-HT receptors and α2-adrenoceptors, and significant contribution of GABA and opioid receptors to the anti-allodynic activity have been identified whereas remarkable contribution of opioid receptors and...
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Pain is a physiological unpleasant sensation that associated with actual or potential tissue damage and affects the major part of human population. Numerous modulatory system control pain through a complex process. The drugs that regulate... more
Pain is a physiological unpleasant sensation that associated with actual or potential tissue damage and affects the major part of human population. Numerous modulatory system control pain through a complex process. The drugs that regulate the modulators involving in this process are currently available; however, the studies to understand the process and develop new agents are still going on. In this review, it is aimed to relay information about how nicotinic receptors contribute the pain modulation. It is obvious that a wide variety of nicotinic receptors is located in both peripheral and central areas. Among these receptors α7, α4β2 and α9α10 receptor subtypes draw attention in terms of pain modulation. The fact that different receptor subtypes involve in different processes of different pain conditions leads to provide beneficial results from the agonism of α7, α4β2 and antagonism of α9α10. The major restraint of the usage of nAChR agonists is their adverse effects. However, nowa...
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Pain is an unpleasant experience comes along with any kind of damage and effects daily routine negatively. Although there are various drugs, many of them could not completely succeed in relieving pain due to pain modulation is a complex... more
Pain is an unpleasant experience comes along with any kind of damage and effects daily routine negatively. Although there are various drugs, many of them could not completely succeed in relieving pain due to pain modulation is a complex process involving numerous mediators and receptors. Therefore, it is a rational approach to identifying the components involved in this complex process and develop new agents act on these components. In this respect, the involvement of muscarinic receptors in pain modulation has drawn attention in recent years. The aim of the review is to exhibit the involvement of the muscarinic receptor subtypes that contribute to pain modulation. The search strategy was performed with MeSH terms and free text words, using the bibliographic databases Science Direct and PubMed. The articles have been collected from the experimental animal studies. It is obvious that muscarinic receptors that are located in both peripheral and central areas are extensively involved i...
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AIMS The aim of this study is to investigate the anxiolytic activity of perampanel, a non-competitive antagonist of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-type glutamate receptors, which is approved for... more
AIMS The aim of this study is to investigate the anxiolytic activity of perampanel, a non-competitive antagonist of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-type glutamate receptors, which is approved for partial-onset seizures in patients with epilepsy, and its mechanism of action. MAIN METHODS The anxiolytic activity of perampanel at the doses of 0.25, 0.5, 1, 2, and 4 mg/kg intraperitoneally (i.p.) was investigated in mice using elevated plus-maze, hole-board, and open-field tests. The findings were compared to the anxiolytic activity of gamma-aminobutyric acid type A benzodiazepine (GABAA/BZ) receptor allosteric modulator diazepam (1 mg/kg, i.p.) and AMPA antagonist GYKI-53655 (5 mg/kg, i.p.). The mechanisms of action of perampanel were evaluated by pre-treatment with GABAA/BZ receptor antagonist flumazenil (3 mg/kg, i.p.), serotonin 5-hydroxytryptamine 1A (5-HT1A) antagonist WAY-100635 (1 mg/kg, i.p.), and α2-adrenoreceptor antagonist yohimbine (5 mg/kg, i.p.). KEY FINDINGS In the elevated plus-maze and open-field tests, perampanel at the dose of 0.5 mg/kg, and in the hole-board test, at the doses of 0.25, 0.5, and 1 mg/kg demonstrated an anxiolytic effect without altering the locomotor activity. The effect of perampanel was comparable to the effect of diazepam. Stimulation of GABAA/BZ and α2-adrenergic receptors contributed to the anxiolytic effect of perampanel, since significant antagonisms were determined in various behavioral parameters by the antagonist pre-treatments. SIGNIFICANCE AMPA antagonism is believed to provide the determined anxiolytic activity of perampanel. Increased GABAergic tonus induced by AMPA receptor antagonism along with other systems, especially the noradrenergic system, might be involved in the anxiolytic activity.
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It is aimed to investigate the central antinociceptive effect of protocatechuic acid and the involvement of stimulation of opioidergic, serotonin 5-HT, α2-adrenergic and muscarinic receptors in protocatechuic acid-induced central... more
It is aimed to investigate the central antinociceptive effect of protocatechuic acid and the involvement of stimulation of opioidergic, serotonin 5-HT, α2-adrenergic and muscarinic receptors in protocatechuic acid-induced central analgesia in mice. Time-dependent antinociceptive effects of protocatechuic acid at the oral doses of 75, 150 and 300 mg/kg were tested in hot-plate (integrated supraspinal response) and tail-immersion (spinal reflex) tests in mice. To investigate the mechanisms of action; the mice administered 300 mg/kg protocatechuic acid (p.o.) were pre-treated with non-specific opioid antagonist naloxone (5 mg/kg, i.p.), serotonin 5-HT receptor antagonist ketanserin (1 mg/kg, i.p.), α2-adrenoceptor antagonist yohimbine (1 mg/kg, i.p.) and non-specific muscarinic antagonist atropine (5 mg/kg, i.p.), respectively. The antinociceptive effect of protocatechuic acid was observed at the doses of 75, 150 and 300 mg/kg in tail-immersion test, at the doses of 150 and 300 mg/kg i...
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This paper focused on evaluating the various biological activities of C. ovata var. palaestina extracts which could beneficially influence diabetes and its complications. </p><p> Methods: Alloxan-induced diabetic BALB-c mice... more
This paper focused on evaluating the various biological activities of C. ovata var. palaestina extracts which could beneficially influence diabetes and its complications. </p><p> Methods: Alloxan-induced diabetic BALB-c mice were administered intraperitoneally with 100, 300, 500mg/kg doses of ethanol and aqueous extracts of buds and fruits. Furthermore, HPLC, phenolic and flavonoid compounds analysis, ABTS and DPPH free radical scavenging activity, anti-inflammatory activity, agar well diffusion and MIC tests were carried out. </p><p> Results: Fruit-aqueous; 100mg/kg, 300mg/kg and bud-aqueous; 500mg/kg extracts showed significant hypoglycemic activity. All extracts indicated important antioxidant activity, however bud-aqueous extract demonstrated the most potent activity. HPLC study exhibited that rutin is found in high amounts in bud-aqueous and bud-ethanol extracts.In further, the bud-aqueous extract depicted stronger and broader antimicrobial activity than...
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Development, in vitro and in vivo evaluation of dexketoprofen trometamol (DT)-loaded nanosized drug delivery system was aimed in this study. DT-loaded solid lipid nanoparticles (SLNs) were prepared using probe sonication. DT release from... more
Development, in vitro and in vivo evaluation of dexketoprofen trometamol (DT)-loaded nanosized drug delivery system was aimed in this study. DT-loaded solid lipid nanoparticles (SLNs) were prepared using probe sonication. DT release from SLNs prepared and their kinetics were investigated. Structures of SLNs were elucidated by particle size and zeta potential measurements, shape and surface imaging, thermal analysis, X-ray diffraction, FT-IR and 1 H-NMR determinations. DT-loaded particles demonstrated characteristic plaque shapes while in vitro release studies showed extended release of DT. Korsmeyer-Peppas kinetic model was found to fit the best using DDSolver software program. Stability, cytotoxicity and in vivo animal experiments were further performed on DT-loaded SLN showing also prolonged analgesic activity in mice. Depending on the in vitro and in vivo test results, formulation developed in this study seems to prolong DT release and is promising for extending analgesic activity.
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Pain is an unpleasant experience and effects daily routine negatively. Although there are various drugs, many of them are not entirely successful in relieving pain, since pain modulation is a complex process involving numerous mediators... more
Pain is an unpleasant experience and effects daily routine negatively. Although there are various drugs, many of them are not entirely successful in relieving pain, since pain modulation is a complex process involving numerous mediators and receptors. Therefore, it is a rational approach to identify the factors involved in the complex process and develop new agents that act on these pain producing mechanisms. In this respect, the involvement of the imidazoline receptors in pain modulation has drawn attention in recent years. In this review, it is aimed to focus on the imidazoline receptors and their ligands which contribute to the pain modulation. It is demonstrated that imidazoline-2 (I2) receptors are steady new drug targets for analgesics. Even if the mechanism of I2 receptor is not well known in the modulation of pain, it is known that it plays a role in tonic and chronic pain but not in acute phasic pain. Moreover, the I2 receptor ligands increase the analgesic effects of opioids in both acute and chronic pain and prevent the development of opioid tolerance. So, they are valuable for the chronic pain treatment and also therapeutic coadjuvants in the management of chronic pain with opiate drugs due to the attenuation of opioid tolerance and addiction. Thus, the use of the ligands which bind to the imidazoline receptors is an effective strategy for relieving pain. This educational forum exhibits the role of imidazoline receptors and ligands in pain process by utilizing experimental studies.
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In the present study chitosan based gel formulations containing Egg Yolk Oil (EYO) and Epidermal Growth Factor (EGF) were formulated successfully aiming at enhanced topical treatment of dermal burns the combination of traditional... more
In the present study chitosan based gel formulations containing Egg Yolk Oil (EYO) and Epidermal Growth Factor (EGF) were formulated successfully aiming at enhanced topical treatment of dermal burns the combination of traditional approaches with modern drug delivery systems. Physicochemical properties of the formulations were analyzed and efficacy of the formulations prepared were evaluated versus a commercial product; Silverdin ® (1% silver sulfadiazine) in vivo on Wistar rats. Burns were generated on the back of the rats and at predetermined time intervals tissue samples were collected and evaluated histologically. The analyses showed that chitosan based gel formulations containing Egg Yolk Oil (E1) and chitosan based gel formulations containing EYO and EGF (M1) formulations seem to be better alternatives for Silverdin ® with a significant difference (p < 0.05) considering healing ranks of tissue samples.
Context: Crataegus species are widely used as herbal medicines for preventing cardiovascular diseases (CVDs). However, there are no studies on the effects of Crataegus monogyna Jacq. (Rosaceae) and C. davisii Browicz on thrombosis, which... more
Context: Crataegus species are widely used as herbal medicines for preventing cardiovascular
diseases (CVDs). However, there are no studies on the effects of Crataegus monogyna Jacq.
(Rosaceae) and C. davisii Browicz on thrombosis, which is an important mechanism in CVDs.
Objective: The purpose of this study was to investigate the antithrombotic effects of ethanol
extracts of Crataegus monogyna (CMEx) and C. davisii (CDEx) leaves by using the carrageenaninduced
tail thrombosis model.
Materials and methods: The hind paw of each mouse was injected with 1% Type I carrageenan
to induce thrombosis. CMEx was tested at the doses of 100, 200, and 300 mg/kg and CDEx at
the dose of 50, 100, 200, and 300 mg/kg in comparison with heparin. The lengths of tail
thrombosis were measured at the 24, 48, and 72 h.
Results: Does of 200 and 300 mg/kg CMEx showed significant effects (p50.01; p50.001) at 24 h
when compared with the control group. The antithrombotic activity of 200 and 300 mg/kg
CMEx showed a decrease at 48 and 72 h but the activity of 300 mg/kg dose of CMEx was still
significant (p50.01). The activities of 50 and 100 mg/kg doses of CDEx were significant
(p50.001; p50.01) between 24 and 72 h whereas 200 and 300 mg/kg CDEx did not show any
significance.
Discussion and conclusions: CMEx and CDEx significantly inhibited the carrageenan-induced
mouse tail thrombosis. Based on these results, it was concluded that CDEx and CMEx may
potentially be used as therapeutic agents or complementary treatments against thrombosis.
diseases (CVDs). However, there are no studies on the effects of Crataegus monogyna Jacq.
(Rosaceae) and C. davisii Browicz on thrombosis, which is an important mechanism in CVDs.
Objective: The purpose of this study was to investigate the antithrombotic effects of ethanol
extracts of Crataegus monogyna (CMEx) and C. davisii (CDEx) leaves by using the carrageenaninduced
tail thrombosis model.
Materials and methods: The hind paw of each mouse was injected with 1% Type I carrageenan
to induce thrombosis. CMEx was tested at the doses of 100, 200, and 300 mg/kg and CDEx at
the dose of 50, 100, 200, and 300 mg/kg in comparison with heparin. The lengths of tail
thrombosis were measured at the 24, 48, and 72 h.
Results: Does of 200 and 300 mg/kg CMEx showed significant effects (p50.01; p50.001) at 24 h
when compared with the control group. The antithrombotic activity of 200 and 300 mg/kg
CMEx showed a decrease at 48 and 72 h but the activity of 300 mg/kg dose of CMEx was still
significant (p50.01). The activities of 50 and 100 mg/kg doses of CDEx were significant
(p50.001; p50.01) between 24 and 72 h whereas 200 and 300 mg/kg CDEx did not show any
significance.
Discussion and conclusions: CMEx and CDEx significantly inhibited the carrageenan-induced
mouse tail thrombosis. Based on these results, it was concluded that CDEx and CMEx may
potentially be used as therapeutic agents or complementary treatments against thrombosis.
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In the present study chitosan based gel formulations containing Egg Yolk Oil (EYO) and Epidermal Growth Factor (EGF) were formulated successfully aiming at enhanced topical treatment of dermal burns the combination of traditional... more
In the present study chitosan based gel formulations containing Egg Yolk Oil (EYO) and Epidermal Growth Factor (EGF) were formulated successfully aiming at enhanced topical treatment of dermal burns the combination of traditional approaches with modern drug delivery systems. Physicochemical properties of the formulations were analyzed and efficacy of the formulations prepared were evaluated versus a commercial product; Silverdin® (1% silver sulfadiazine) in vivo on Wistar rats. Burns were generated on the back of the rats and at predetermined time intervals tissue samples were collected and evaluated histologically. The analyses showed that chitosan based gel formulations containing Egg Yolk Oil (E1) and chitosan based gel formulations containing EYO and EGF (M1) formulations seem to be better alternatives for Silverdin® with a significant difference (p < 0.05) considering healing ranks of tissue samples.
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Benzimidazole 5-carboxylic acid derivatives were investigated for analgesic activity in this study. Of the benzimidazole compounds tested, 2-(2-nitro-phenyl)-1H-benzimidazole 5-carboxylic acid showed remarkable naloxone sensitive... more
Benzimidazole 5-carboxylic acid derivatives were investigated for analgesic activity in this study. Of the benzimidazole compounds tested, 2-(2-nitro-phenyl)-1H-benzimidazole 5-carboxylic acid showed remarkable naloxone sensitive analgesic activity in the tail clamp but not in the tail immersion analgesia tests. This centrally active compound showed antispasmodic activity only on KCl induced contractions of isolated rat ileum and not on acetylcholine induced contractions. Acute toxicity of the compounds were >100 mg/kg i.p. mice. It was concluded that substitution of the 2(o-phenyl) by nitro- but not by chloro- or methoxy groups is important for naloxone sensititive analgesic activity of benzimidazole compounds and it was hypothetized that new imidazole compounds having a 2-(o-substituted phenyl) moiety needs to be investigated.