scholarly journals Novel nociceptin analogues.

2001 ◽  
Vol 48 (4) ◽  
pp. 1155-1158
Author(s):  
H Bartosz-Bechowski ◽  
R Miedzybrodzki ◽  
S Szymaniec
Keyword(s):  
Sulfhydryl Group ◽  
Tail Flick ◽  
Tail Flick Test ◽  
In Vivo Tests

A series of new nociceptin analogues containing cysteine was tested for their nociceptive effects in tail-flick test on mice after icv injection. The cysteines were introduced in order to get irreversibly binding analogues based on the assumption that the cysteines in the ligand can interact with the cysteines from the receptor to form an S-S bridge. In vivo tests revealed that Cys1-nociceptin (1-13)-NH2 (Cys1-NC) is an antagonist, whereas Cys7-NC is an agonist. Gly1[Phe(p-NO2)]4-NC was less active indicating that the antagonist properties of Cys1-NC are associated with the presence of the sulfhydryl group of cysteine. The analogues D-Cys2 and Cys3 were also almost inactive.

Prolonged Anti-Inflammatory Activity of Topical Melatonin by Niosomal Encapsulation

2014 ◽  
Vol 902 ◽  
pp. 70-75 ◽  
Author(s):  
Aroonsri Priprem ◽  
Vassana Netweera ◽  
Pramote Mahakunakorn ◽  
Nutjaree Pratheepawanit Johns ◽  
Jeffrey Roy Johns
Keyword(s):  
Skin Permeation ◽  
Entrapment Efficiency ◽  
Rapid Decline ◽  
Tail Flick ◽  
Tail Flick Test ◽  
Topical Gel ◽  
Anti Inflammatory ◽  
Average Size

Melatonin, encapsulated and non-encapsulated, in a topical gel, was comparatively investigated for its in vitro permeation and in vivo anti-inflammatory properties. An average size of the melatonin-encapsulated niosomes of 197 nm with a zeta potential of-78.8 mV and an entrapment efficiency of 92.7% was incorporated into a gel base. In vitro skin permeation of the same gel base incorporated with non-encapsulated melatonin or melatonin niosomes at 5% was comparatively evaluated through porcine skin using Franz diffusion cells and analyzed by spectroflurometry at λex 278 and λem 348 nm. From the same gel base, the permeation rate of non-encapsulated melatonin was about 2.5 times greater than that of melatonin-encapsulated niosomes. In comparison to piroxicam gel and hydrocortisone cream used as the positive controls, topical applications of melatonin and melatonin niosome gels tested in croton oil-induced ear edema in mice suggested that its anti-inflammatory activities were prolonged by the niosomal encapsulation. Similarly, analgesic effect of melatonin was prolonged by niosomal encapsulation using tail flick test in mice. Therefore, its immediate permeation through the skin was retarded by niosomal encapsulation which could also prolong its rapid decline in exerting anti-inflammatory and analgesic activities in vivo.

scholarly journals Discovery of Orexant and Anorexant Agents with Indazole Scaffold Endowed with Peripheral Antiedema Activity

Biomolecules ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. 492 ◽  
Author(s):  
Dimmito ◽  
Stefanucci ◽  
Pieretti ◽  
Minosi ◽  
Dvorácskó ◽  
...  
Keyword(s):  
Feeding Behavior ◽  
Cannabinoid Receptors ◽  
Cannabinoid Receptor ◽  
Methyl Esters ◽  
Endocannabinoid System ◽  
Tail Flick ◽  
Binding Assays ◽  
Tail Flick Test

The endocannabinoid system represents an integrated neuronal network involved in the control of several organisms’ functions, such as feeding behavior. A series of hybrids of 5-(4-chlorophenyl)-1-(2,4-dichloro-phenyl)-4-methyl-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide (mimonabant), a well-known inverse agonist of the type-1 cannabinoid receptor (CB1), once used as an antiobesity drug, and the N-(2S)-substitutes of 1-[(4-fluorophenyl)methyl]indazole-3-carboxamide with 1-amino-3-methyl-1-oxobutane (AB-Fubinaca), 1-amino-3,3-dimethyl-1-oxobutane (ADB-Fubinaca), and 3-methylbutanoate (AMB-Fubinaca), endowed with potent agonistic activity towards cannabinoid receptors CB1 and CB2 were in solution as C-terminal amides, acids, methyl esters and N-methyl amides. These compounds have been studied by binding assays to cannabinoid receptors and by functional receptor assays, using rat brain membranes in vitro. The most active among them as an agonist, (S)-1-(2,4-dichlorobenzyl)-N-(3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl)-1H-indazole-3-carboxamide (LONI11), and an antagonist, (S)-2-(1-(2,4-dichlorobenzyl)-1H-indazole-3-carboxamido)-3-methylbutanoic acid (LONI4), were tested in vivo in mic, to evaluate their ability to stimulate or suppress feeding behavior after intraperitoneal (i.p.) administration. For a LONI11 formalin test and a tail flick test after an administration by the subcutaneous (s.c.) and intracerebroventricular (i.c.v.) routes, respectively, were also carried out in vivo in mice to investigate the antinociceptive property at the central and peripheral levesl. We observed a significant orexant effect for LONI11 and an intense anorexant effect for (S)-methyl 2-(1-(2,4-dichlorobenzyl)-1H-indazole-3-carboxamido)-3,3-dimethylbutanoate (LONI2) and LONI4. In zymosan-induced edema and hyperalgesia, LONI11 reduced the percent of paw volume increase and paw latency after s.c. administration, also suggesting a possible peripheral anti-inflammatory activity.

scholarly journals A systematic review of traditionally used herbs and animal-derived products as potential analgesics

2020 ◽  
Vol 18 ◽  
Author(s):  
Kannan RR Rengasamy ◽  
Mohamad Fawzi Mahomoodally ◽  
Teshika Joaheer ◽  
Yansheng Zhang
Keyword(s):  
Literature Search ◽  
Relevant Information ◽  
The Body ◽  
In Vivo Studies ◽  
Tail Flick ◽  
Indigenous Plants ◽  
Tail Flick Test ◽  
Animal Products ◽  
Future Studies

: Pain is a distressing but fundamental manifestation that prepares the body for potentially detrimental stimuli while ensuring its protection. Plant and animal products have traditionally been used to relieve pain for centuries. However, no attempt has been made to compile a single report of plant and animal products possessing analgesic properties. This review enadeavours to recover data from published articles to establish a collective literature review on folk remedies from plant and animal sources used as analgesics and in the treatment of pain-related conditions, identifying gaps in existing knowledge and future works. Relevant information was systematically retrieved using the PRISMA method. In this review, in total, 209 plants were found to be either used raw or prepared by decoctions or maceration. Administration was either oral or topical, and they were predominantly used in Asian countries. In vivo studies of plants with analgesic properties, which were tested using different methods including acetic-induced writhing test, hotplate test, tail-flick test, and formalin-induced pain test, were compiled. Animal products with analgesic properties were obtained mainly from compounds present in venom; their bioactive compounds were also identified. In the literature search, certain gaps were noted, which could be reviewed in future studies. For instance, there was a disparity of information regarding the traditional uses of medicinal plants. In this review, an attempt was made to critically assess and describe the pharmacological properties and bioactive composition of indigenous plants, some animal species, and animal venom by scrutinizing databases and looking for published articles. Therefore, it can be concluded that the compounds obtained from these sources can serve as important ingredients in therapeutic agents to alleviate pain once their limitations are assessed and improved upon. In the literature search, certain gaps were noted, which could be reviewed in future studies.

scholarly journals Discovery of a New Analgesic Peptide, Leptucin, from the Iranian Scorpion, Hemiscorpius lepturus

Molecules ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 2580
Author(s):  
Sedigheh Bagheri-Ziari ◽  
Delavar Shahbazzadeh ◽  
Soroush Sardari ◽  
Jean-Marc Sabatier ◽  
Kamran Pooshang Bagheri
Keyword(s):  
Venom Gland ◽  
Preclinical Study ◽  
Scorpion Venom ◽  
Tail Flick ◽  
Tail Flick Test ◽  
Analgesic Peptides ◽  
Epidemiological Surveys ◽  
Scorpion Stings ◽  
Hemiscorpius Lepturus

Hemiscorpius lepturus scorpion stings do not induce considerable pain based on epidemiological surveys conducted in the southwest part of Iran. Accordingly, this study was aimed to identify the analgesic molecule in H. lepturus venom by analyzing a cDNA library of the scorpion venom gland looking for sequences having homology with known animal venom analgesic peptides. The analgesic molecule is a cysteine rich peptide of 55 amino acids. the synthetic peptide was deprotected and refolded. RP-HPLC, Ellman’s, and DLS assays confirmed the refolding accuracy. Circular dichroism (CD) showed helix and beta sheet contents. This peptide, called leptucin, demonstrated 95% analgesic activity at the dose of 0.48 mg/kg in hot plate assay. Leptucin at the doses of 0.32, 0.48, and 0.64 mg/kg showed 100% activity in thermal tail flick test. No hemolysis or cytotoxicity was observed at 8 and 16 µg. Histopathology evaluations indicated no hepatotoxicity, nephrotoxicity, and cardiotoxicity. We thus report that leptucin is the analgesic agent of H. lepturus venom. Regarding the high in vivo efficacy of leptucin and the fact it shows no observable toxicity, it could be suggested as a drug lead in a preclinical study of acute pain as well as the study of its mechanism of action.

scholarly journals The Quaternary Lidocaine Derivative, QX-314, Produces Long-lasting Local Anesthesia in Animal Models In Vivo 

2007 ◽  
Vol 107 (2) ◽  
pp. 305-311 ◽  
Author(s):  
Tony K. Y. Lim ◽  
Bernard A. MacLeod ◽  
Craig R. Ries ◽  
Stephan K. W. Schwarz
Keyword(s):  
Animal Models ◽  
Sciatic Nerve ◽  
Local Anesthesia ◽  
Local Anesthetic ◽  
Tail Flick ◽  
Motor Blockade ◽  
Tail Flick Test ◽  
Sensory Blockade ◽  
Long Duration

Background QX-314 is a quaternary lidocaine derivative considered to be devoid of clinically useful local anesthetic activity. However, several reports document that extracellular QX-314 application affects action potentials. Hence, the authors tested the hypothesis that QX-314 could produce local anesthesia in animal models in vivo. Methods The authors tested QX-314 (10, 30, and 70 mM) in three standard in vivo local anesthetic animal models, using a randomized, blinded experimental design with negative (placebo) and positive (70 mM lidocaine) controls. The guinea pig intradermal wheal assay (n = 29) was used to test for peripheral inhibition of the cutaneous trunci muscle reflex, the mouse tail-flick test (n = 30) was used to test for sensory blockade, and the mouse sciatic nerve blockade model (n = 45) was used to test for motor blockade. Results In all three animal models, QX-314 concentration-dependently and reversibly produced local anesthesia of long duration, at concentrations equivalent to those clinically relevant for lidocaine. In the guinea pig intradermal wheal assay, QX-314 produced peripheral nociceptive blockade up to 6 times longer than lidocaine (650 +/- 171 vs. 100 +/- 24 min [mean +/- SD]; n = 6 per group; P < 0.0001). In the mouse tail-flick test, QX-314 produced sensory blockade up to 10 times longer than lidocaine (540 +/- 134 vs. 50 +/- 11 min; n = 6 per group; P < 0.0001). Finally, in the mouse sciatic nerve model, QX-314 produced motor blockade up to 12 times longer compared with lidocaine (282 +/- 113 vs. 23 +/- 10 min; n = 9 or 10 per group; P < 0.0001). The onset of QX-314-mediated blockade was consistently slower compared with lidocaine. Animals injected with saline exhibited no local anesthetic effects in any of the three models. Conclusion In a randomized, controlled laboratory study, the quaternary lidocaine derivative, QX-314, concentration-dependently and reversibly produced long-lasting local anesthesia with a slow onset in animal models in vivo. The authors' results raise the possibility that quaternary ammonium compounds may produce clinically useful local anesthesia of long duration in humans and challenge the conventional notion that these agents are ineffective when applied extracellularly.

Intrathecal Catheterization in the Rat

1996 ◽  
Vol 85 (5) ◽  
pp. 1184-1189 ◽  
Author(s):  
Shinichi Sakura ◽  
Keishi Hashimoto ◽  
Andrew W. Bollen ◽  
Ricardo Ciriales ◽  
Kenneth Drasner
Keyword(s):  
Sensory Function ◽  
In Vivo Model ◽  
Tail Flick ◽  
Tail Flick Test ◽  
Original Length ◽  
Catheterization Technique ◽  
Significant Difference ◽  
Intrathecal Drug Administration ◽  
Morphologic Changes

Background The authors previously described an in vivo model suitable for investigation of functional impairment induced by intrathecally injected local anesthetic. However, meaningful histologic analysis could not be performed because catheterization, per se, induced morphologic changes in control animals. In the current experiments, the authors sought to identify an alternative, less reactive, catheterization technique for intrathecal drug administration. Methods Twenty-five rats received an intrathecal infusion of normal saline through a catheter composed of either 28-gauge polyurethane, 32-gauge polyimide, 32-gauge polyurethane, PE-10 polyethylene, or PE-10 polyethylene that had been stretched to twice its original length. Seven days after infusion, sensory function was assessed using the tail-flick test, and the spinal cord and nerve roots were prepared for neuropathologic evaluation. Results There was no significant difference in sensory function among groups. Animals in which 28-gauge polyurethane, 32-gauge polyimide, PE-10, and double-stretched PE-10 had been implanted had moderate to severe nerve injury in 11%, 14%, 23%, and 8% of fascicles, respectively, whereas none of the animals in which 32-gauge polyurethane was implanted had any evidence of moderate or severe damage. Conclusions Morphologic changes induced by intrathecal catheterization in the rat can be minimized by the use of 32-gauge polyurethane tubing.

scholarly journals Effects ofBrugmansia arboreaExtract and Its Secondary Metabolites on Morphine Tolerance and Dependence in Mice

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Laura Mattioli ◽  
Antonio Bracci ◽  
Federica Titomanlio ◽  
Marina Perfumi ◽  
Vincenzo De Feo
Keyword(s):  
Secondary Metabolites ◽  
Therapeutic Potential ◽  
Morphine Tolerance ◽  
Opioid Addiction ◽  
Withdrawal Symptoms ◽  
Morphine Dependence ◽  
Tail Flick ◽  
Tail Flick Test

The aim of the present study was to investigate,in vivo, the effect of aBrugmansia arboreaextract (BRU), chromatographic fractions (FA and FNA), and isolated alkaloids on the expression and the acquisition of morphine tolerance and dependence. Substances were acutely (for expression) or repeatedly (for acquisition) administered in mice treated with morphine twice daily for 5 or 6 days, in order to make them tolerant or dependent. Morphine tolerance was assessed using the tail-flick test at 1st and 5th days. Morphine dependence was evaluated through the manifestation of withdrawal symptoms induced by naloxone injection at 6th day. Results showed that BRU significantly reduced the expression of morphine tolerance, while it was ineffective to modulate its acquisition. Chromatographic fractions and pure alkaloids failed to reduce morphine tolerance. Conversely BRU, FA, and pure alkaloids administrations significantly attenuated both development and expression of morphine dependence. These data suggest thatBrugmansia arboreaLagerh might have human therapeutic potential for treatment of opioid addiction.

scholarly journals Preparation and In Vivo Evaluation of a Lidocaine Self-Nanoemulsifying Ointment with Glycerol Monostearate for Local Delivery

Pharmaceutics ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1468
Author(s):  
Ji-Hyun Kang ◽  
Kwang-Hwi Yoo ◽  
Hyo-Young Park ◽  
Seung-Min Hyun ◽  
Sang-Duk Han ◽  
...  
Keyword(s):  
Local Anesthetic ◽  
The Self ◽  
In Vitro Dissolution ◽  
Tail Flick ◽  
Glycerol Monostearate ◽  
Depth Of Penetration ◽  
Tail Flick Test ◽  
Anesthetic Effect

Lidocaine, a commonly used local anesthetic, has recently been developed into a number of ointment products to treat hemorrhoids. This study examined its efficient delivery to the dermis through the pharmaceutical improvement of hemorrhoid treatment ointments. We attempted to increase the amount of skin deposition of lidocaine by forming a nanoemulsion through the self-nanoemulsifying effect that occurs when glycerol monostearate (GMS) is saturated with water. Using Raman mapping, the depth of penetration of lidocaine was visualized and confirmed, and the local anesthetic effect was evaluated via an in vivo tail-flick test. Evaluation of the physicochemical properties confirmed that lidocaine was amorphous and evenly dispersed in the ointment. The in vitro dissolution test confirmed that the nanoemulsifying effect of GMS accelerated the release of the drug from the ointment. At a specific concentration of GMS, lidocaine penetrated deeper into the dermis; the in vitro permeation test showed similar results. When compared with reference product A in the tail-flick test, the L5 and L6 compounds containing GMS had a significantly higher anesthetic effect. Altogether, the self-nanoemulsifying effect of GMS accelerated the release of lidocaine from the ointment. The compound with 5% GMS, the lowest concentration that saturated the dermis, was deemed most appropriate.

Lidocaine-loaded reduced graphene oxide hydrogel for prolongation of effects of local anesthesia: In vitro and in vivo analyses

2021 ◽  
Vol 35 (8) ◽  
pp. 1034-1042
Author(s):  
Weifan Li ◽  
Guangqi Zhang ◽  
Xiaoxia Wei
Keyword(s):  
Graphene Oxide ◽  
Reduced Graphene Oxide ◽  
Local Anesthesia ◽  
Ex Vivo ◽  
Tail Flick ◽  
Tail Flick Test ◽  
Duration Of Action ◽  
Reduced Graphene

Lidocaine is widely used as a local anesthetic for alleviation of post-operative pain and for management of acute and chronic painful conditions. Although several approaches are currently used to prolong the duration of action, an effective strategy to achieve neural blockage for several hours remains to be identified. In this study, a lidocaine-loaded Pluronic® F68-reduced graphene oxide hydrogel was developed to achieve sustained release of lidocaine. Fourier transform infrared spectroscopy, X-ray diffraction, and Raman spectroscopy confirmed the synthesis of Pluronic® F68-reduced graphene oxide. Transmission electron microscopy showed wrinkled, flat nanosheets with micelles attached. The developed hydrogel showed desirable pH, viscosity, adhesiveness, hardness, and cohesiveness for topical application. The ex vivo release study demonstrated the ability of the Pluronic® F68-reduced graphene oxide hydrogel to prolong release up to 10 h, owing to the strong π–π interactions between the graphene oxide and the lidocaine. In comparison with a commercial lidocaine ointment, the developed graphene oxide hydrogel showed sustained anesthetic effect in the radiant heat tail flick test and sciatic nerve block model. Thus, this study demonstrates the potential of using Pluronic® F68-reduced graphene oxide nanocarriers to realize prolonged effects of local anesthesia for effective pain management.

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