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1.
The objective of this study was to evaluate the pharmacological antihyperalgesic interaction between N‐palmitoylethanolamide (PEA) and acetaminophen in diabetic rats using the formalin paw test. Streptozotocin (STZ)‐induced diabetic rats received subcutaneous injections in the paw of PEA alone (1–100 μg/paw) or acetaminophen alone (3–300 μg/paw) 15 min before formalin (0.5%) injection. The results revealed concentration‐dependent responses produced by PEA (EC 50 = 7.19 ± 0.7 μg/paw) and acetaminophen (EC 50 = 57.9 ± 1.9 μg/paw). Isobolographic analysis was used to evaluate the pharmacological interaction between the PEA + acetaminophen using the EC 50 value and a fixed 1:1 ratio combination. The isobologram demonstrated that the combination investigated in this study produced a synergistic interaction; the experimental value (EC 50= 23.64 ± 1.9 μg/paw) was significantly smaller than those that resulted from theoretical calculations (EC 50 = 32.56 μg/paw). These results provide evidence that PEA in combination with acetaminophen could be useful for pain therapy in neuropathic diabetic patients. Drug Dev Res 76 : 228–234, 2015. © 2015 Wiley Periodicals, Inc. 相似文献
2.
The present study was designed to evaluate the possible antinociceptive interaction between diacerhein and some antiepileptic drugs (carbamazepine, topiramate and gabapentin) on formalin‐induced nociception. Diacerhein, each of the antiepileptics or a fixed dose‐ratio combination of these drugs was assessed after local peripheral and oral administration in rats. lsobolographic analyses were used to define the interaction between drugs. Diacerhein, antiepileptic drugs (carbamazepine, topiramate and gabapentin) or their combinations yielded a dose‐dependent antinociceptive effect when administered by both routes. Theoretical ED 30 values for the combination estimated from the isobolograms were obtained as follows: diacerhein‐carbamazepine (85.99 ± 7.07 μg/paw; 56.53 ± 4.56 mg/kg po), diacerhein‐topiramate (197.97 ± 22.90 μg/paw; 13.06 ± 2.44 mg/kg po) and diacerhein‐gabapentin (96.87 ± 17.73 μg/paw; 17.90 ± 4.70 mg/kg p.o.) for the local peripheral and oral administration routes, respectively. These values were significantly higher than the experimentally obtained ED 30 values: diacerhein‐carbamazepine (49.33 ± 3.37 μg/paw; 35.49 ± 7.91 mg/kg po), diacerhein‐topiramate (133.00 ± 39.10 μg/paw; 8.87 ± 1.46 mg/kg po) and diacerhein‐gabapentin (70.98 ± 14.73 μg/paw; 10.95 ± 3.23 mg/kg po). The combinations produced their antinociceptive effects without motor impairment in the rotarod test indicating synergistic interactions with a good side effect profile. 相似文献
3.
Systemic coadministration of tramadol and dexketoprofen can produce antinociceptive synergism in animals. There has been only limited evaluation of this drug combination in the peripheral nervous system in terms of the antinociceptive interaction and its mechanisms. The aim of the present study was to evaluate the peripheral antinociceptive interaction between tramadol and dexketoprofen in the formalin test and the involvement of the nitric oxide (NO)–cyclic guanosine monophosphate pathway and ATP‐sensitive K + channels. Different doses of tramadol or dexketoprofen were administered locally to the formalin‐injured mouse paw and the antinociceptive effect evaluated. ED 50 values were calculated for both drugs alone and in combination. Coadministration of tramadol and dexketoprofen produced an antinociceptive synergistic interaction during the second phase of the formalin test. Pretreatment with NO antagonists, including l ‐NG‐nitroarginine methyl ester and 1H‐[1,2,4]‐oxadiazolo‐[4,3‐a]‐quinoxalin‐1‐one, or the ATP‐sensitive K + channel antagonist glibenclamide reversed the antinociceptive synergistic effect of the tramadol–dexketoprofen combination, suggesting that NO and ATP‐sensitive K + channels were involved. 相似文献
4.
Gabapentin is an anticonvulsant used to treat neuropathic pain. Mangiferin is an antioxidant that has antinociceptive and antiallodynic effects in inflammatory and neuropathic pain models. The purpose of this study was to determine the interaction between mangiferin and gabapentin in the development and maintenance of formalin‐induced secondary allodynia and hyperalgesia in rats. Gabapentin, mangiferin, or their fixed‐dose ratio combination were administrated peripherally. Isobolographic analyses was used to define the nature of the interaction of antiallodynic and/or antihyperalgesic effects of the two compounds. Theoretical ED 50 values for the combination were 74.31 µg/paw and 95.20 µg/paw for pre‐ and post‐treatment, respectively. These values were higher than the experimental ED 50 values, 29.45 µg/paw and 37.73 µg/paw respectively, indicating a synergistic interaction in formalin‐induced secondary allodynia and hyperalgesia. The antiallodynic and antihyperalgesic effect induced by the gabapentin/mangiferin combination was blocked by administration of L‐NAME, the soluble guanylyl cyclase inhibitor, ODQ and glibenclamide. These data suggest that the gabapentin‐ mangiferin combination produces a synergistic interaction at the peripheral level. Moreover, the antiallodynic and hyperalgesic effect induced by the combination is mediated via the activation of an NO‐cyclic GMP‐ATP‐sensitive K + channel pathway. Drug Dev Res 78 : 390‐402, 2017. © 2017 Wiley Periodicals, Inc. 相似文献
5.
The aim of this study was to evaluate the interaction between tramadol and parecoxib in the orofacial formalin test. Tramadol (10, 31.6, 56, and 100 mg/kg ip) or parecoxib (31.6, 56, 100, and 178 mg/kg ip) were administered 10 min before formalin (2.5%) injection into the upper lip to characterize the dose–response curve of each individual drug in the orofacial pain test in mice. Once the dose–response curve of each drug was obtained, an experimental effective dose 50 (ED 50) value was determined for each drug. The tramadol–parecoxib combination was evaluated in four different groups of animals. The isobolographic analysis and the interaction index were used to evaluate the nature of interaction between both drugs. The isobologram and the interaction index showed increased in the antinociceptive effect of the combination. The tramadol–parecoxib combination produces a synergism in the second phase of the orofacial formalin test. Drug Dev Res 73 : 152–156, 2015. © 2015 Wiley Periodicals, Inc. 相似文献
6.
Analgesics with different mechanisms of action can be combined in order to obtain pharmacological synergism, employing lower doses of each agent, thus diminishing side effects. For instance, an atypical dual analgesic such as tramadol (TMD) and a nonsteroidal anti‐inflammatory drug such as ibuprofen (IBU) are good candidates to be evaluated when combined and applied peripherally. The present study was conducted to evaluate possible local synergism between TMD and IBU when combined peripherally using the formalin test in rats. The effects of the individual analgesics and their combinations were evaluated simultaneously using a 5% formalin dilution. Dose–effect curves were determined for TMD (50–400 μg/paw) and IBU (1–100 μg/paw). Experimental effective doses were evaluated and isobolographic analyses were constructed to evaluate TMD‐IBU combination synergism. Both drugs produced a dose‐dependent analgesic effect when applied separately. Isobolographic analysis showed synergism during phase 1 (0–10 min) and phase 2 (15–60 min) when compared with theoretical doses ( P < 0.05), with interaction indexes of 0.06 and 0.09, respectively. The present information supports the peripheral analgesic effect of TMD and IBU, especially when combined at appropriate doses. 相似文献
7.
Objectives The present study examined the mechanisms involved in the antinociceptive effects of bis selenide [(Z)‐2,3‐bis(4‐chlorophenylselanyl)prop‐2‐en‐1‐ol]. Methods The effects of oral bis selenide were tested against licking behaviour and oedema in mice induced by formalin, serotonin, histamine, glutamate, phorbol 12‐myristate 13‐acetate (PMA), 8‐bromoadenosine 3′,5′‐cyclic monophosphate (8‐BrcAMP) and pros‐taglandin E 2. The effects of a variety of receptor antagonists on the antinociceptive activity were tested to determine the likely mechanism of action of bis selenide. Key findings Bis selenide caused antinociception on the first and second phases of the formalin test, with mean ID50 values of 34.21 (29.66–39.45) and 15.86 (12.17–20.67) mg/kg and maximal inhibition of 65 ± 3% and 90 ± 1%, respectively. At 50 mg/kg bis selenide significantly inhibited (31 ± 2%) paw oedema induced by intraplantar injection of formalin. At 25 mg/kg given 5 min after the formalin injection, bis selenide caused a significant inhibition (42 ± 5%) in the second phase of the formalin test, whereas the prophylactic treatment caused more intense inhibition (64 ± 3%). Oral administration of bis selenide reduced licking and paw oedema induced by serotonin, histamine, glutamate, PGE 2, PMA and 8‐BrcAMP. The antinociceptive effect of bis selenide (25 mg/kg, p.o.) on the formalin test was reversed by i.p. administration of p‐chlorophenylalanine methyl ester (an inhibitor of serotonin synthesis), ketanserin (a selective 5‐HT 2a receptor antagonist), ondansetron (a 5‐HT 3 receptor antagonist) and ranitidine (a histamine H 2‐receptor antagonist). Conclusions Glutamatergic, prostaglandin E 2, serotonergic (5‐HT 2a and 5‐HT 3) and histamine H 2 receptors are involved in the antinociceptive effects of bis selenide in mice. The interaction of bis selenide with protein kinase C and A signalling pathways was also demonstrated. 相似文献
8.
The purpose of this study was to evaluate the antinociceptive interaction between acetaminophen and lysine clonixinate in the formalin test, and the possible role of opioidergic and nitric oxide pathways in the interaction. The effect of individual drugs and their combination was evaluated using the 3% formalin test in mice. Acetaminophen (31.6, 100, 178, and 316 mg/kg, i.p.) or lysine clonixinate (5.6, 10, 17.8, and 31.6 mg/kg, i.p.) were administered 10 min before formalin injection. To assess the possible mechanism(s) of action for the combination, naloxone (1 mg/kg) and N (G)‐nitro‐L‐arginine methyl ester (L‐NAME) (3 mg/kg) were used. Isobolographic analysis and the interaction index showed a synergistic effect. The experimental ED 30 was lower when compared with theoretical ED 30. Naloxone, but not L‐NAME, reduced the antinociceptive effect of the combination. Administration of antagonists alone did not modify formalin‐induced nociception. These data suggest that the acetaminophen–lysine clonixinate combination produces a synergistic effect involving opioid receptors. 相似文献
9.
The relationship between blood levels of ketoprofen and its anti‐hyperalgesic effects was examined in rat using the carrageenan‐evoked thermal hyperalgesia model. Female adult Wistar rats were injected with carrageenan into the plantar surface of the right hind paw. Immediately after, rats were administered with ketoprofen po and hindpaw withdrawal latency measured and micro‐whole blood samples were obtained over six hours via a cannula inserted in the caudal artery. Ketoprofen levels were measured by HPLC. Ketoprofen concentration increased in a dose‐dependent manner and was reflected in dose‐dependent anti‐hyperalgesic effect. The pharmacokinetic and pharmacodynamic parameters expressed as mean ± s.e.m. following administration of 1, 3.2, and 10 mg/kg ketoprofen were: C max 1.27 ± 0.08, 3.44 ± 0.20 and 11.76 ± 0.81 μg/mL; AUC last 4.16 ± 0.17, 11.63 ± 0.65 and 28.15 ± 1.32 μg h/mL; and E max observed (AUC E): 65.41 ± 7.79, 92.06 ± 6.46 and 98.42 ± 7.53%. A direct relationship between blood concentrations and the anti‐hyperalgesic effect of ketoprofen followed a maximum effect model equation. The results indicate that the anti‐hyperalgesic effect of ketoprofen in the carrageenan pain model can be predicted by the pharmacokinetic properties of ketoprofen. 相似文献
10.
The diterpene ent‐dihydrotumanoic acid (DTA) was among the compounds isolated from Gymnosperma glutinosum (Spreng) Less (Asteraceae). There are no reports regarding the pharmacological effects of DTA. Cytotoxicity against cancer cells (1–250 µM), and the antibacterial (50–1400 µM) activity of DTA were evaluated using the MTT assay, and the minimum inhibitory concentration test, respectively. The antidiarrheal (1–100 mg/kg p.o.) and anti‐inflammatory (2 mg/ear) effects of DTA were evaluated using castor oil and 12 ‐O‐ tetradecanoylphorbol ‐ 13 ‐ acetate, respectively. The antinociceptive and sedative effects of DTA (1–100 mg/kg p.o.) were evaluated using two models of chemically‐induced nociception, and the pentobarbital‐induced sleeping time test, respectively. The antinociceptive mechanism of DTA was evaluated using the acetic acid writhing test with inhibitors related to pain processing pathways. The effects of DTA (10–100 mg/kg p.o.) on locomotor activity were evaluated using the rotarod test. DTA lacked cytotoxic activity (IC 50 > 100 µM) on cancer cells, possessed moderate antibacterial effects against B. subtillis (MIC= 175 µM), moderate antidiarrheal and anti‐inflammatory effects, and minimal vasorelaxant effects. In the formalin test, DTA showed antinociceptive effects in both phases. In the acetic acid test, DTA showed antinociceptive activity (ED 50= 50.2 ± 5.6 mg/kg) with potency similar to that of naproxen (NPX; ED 50=33.7 ± 4.5 mg/kg) an effect blocked by naloxone implicating an opioid mechanism. DTA also exerted antidiarrheal activity and showed no sedative effects or changes in locomotor activity in mice. Drug Dev Res 78 : 340‐348, 2017. © 2017 Wiley Periodicals, Inc. 相似文献
11.
The aim of the present study was to evaluate the antinoceptive interaction between the opioid analgesic, tapentadol, and the NSAID, ketorolac, in the mouse orofacial formalin test. Tapentadol or ketorolac were administered ip 15 min before orofacial formalin injection. The effect of the individual drugs was used to calculate their ED 50 values and different proportions (tapentadol‐ketorolac in 1:1, 3:1, and 1:3) were assayed in the orofacial test using isobolographic analysis and interaction index to evaluate the interaction between the drugs. The combination showed antinociceptive synergistic and additive effects in the first and second phase of the orofacial formalin test. Naloxone and glibenclamide were used to evaluate the possible mechanisms of action and both partially reversed the antinociception produced by the tapentadol‐ketorolac combination. These data suggest that the mixture of tapentadol and ketorolac produces additive or synergistic interactions via opioid receptors and ATP‐sensitive K + channels in the orofacial formalin‐induced nociception model in mice. Drug Dev Res 78 : 63–70, 2017. © 2016 Wiley Periodicals, Inc. 相似文献
12.
Metformin‐dependent mechanisms have been implicated in the antinociceptive effect of some non‐steroidal anti‐inflammatory drugs (NSAIDs). In this study, the effect of local peripheral or systemic administration of metformin on the local peripheral or systemic antinociception induced by indomethacin, ketorolac and metamizole was assessed in the rat carrageenan‐induced thermal hyperalgesia model. Rats were injected with carrageenan (1%, 50 µl) into the right hindpaw which reduced paw withdrawal latency, a measure of thermal hyperalgesia. Local peripheral or systemic administration of indomethacin, ketorolac or metamizole dose‐dependently reduced carrageenan‐induced thermal hyperalgesia. Local peripheral pre‐treatment with metformin (800 µg/paw) partially inhibited the anti‐hyperalgesic effect of indomethacin (200 µg/paw) and metamizole (200 µg/paw), but not that of ketorolac (200 µg/paw). In contrast, systemic pre‐treatment with metformin (200 mg/kg) attenuated the antihyperalgesic effect of metamizole (10 mg/kg), but not that observed with either indomethacin (10 mg/kg) or ketorolac (10 mg/kg). These findings suggest that some but not all NSAIDs have effects mediated by metformin‐dependent mechanisms. Drug Dev Res 78 : 98–104, 2017. ©2017 Wiley Periodicals, Inc. 相似文献
13.
This study was conducted to investigate the analgesic activities and mechanism of anti‐inflammatory activities of a 50% ethanol extract of Taxillus tsaii (ETT) in vivo using the acetic acid induced writhing test and formalin induced paw licking in mice. The anti‐inflammatory effect of ETT was evaluated using a mouse model of λ‐carrageenan (Carr)‐induced paw edema. ETT reduced the writhing in the acetic acid assay test at a dose 1.0 g/kg po and reduced the licking time in the late phase of the formalin test at doses of 0.5 and 1.0 g/kg po). Carr‐induced paw edema was reduced when ETT (0.5 and 1.0 g/kg po) was administered 3–5 h after Carr injection. ETT (1.0 g/kg po) reduced the level of malondialdehyde in the edemic paw by increasing the activity of antioxidant enzymes, e.g., superoxide dismutase and glutathione reductase, in the liver and reducing TNF‐α, IL‐1β, and IL‐6 activity in the edemic paw. This study demonstrates the analgesic and anti‐inflammatory effects of ETT, thus verifying its application in traditional Chinese medicine. Drug Dev Res 76 : 176–184, 2015. © 2015 Wiley Periodicals, Inc. 相似文献
14.
1. The aim of the present study was to explore the concept of multimodal anaesthesia using a combination of two non‐opioid analgesics, namely nefopam, a centrally acting non‐opioid that inhibits monoamine reuptake, and paracetamol, an inhibitor of central cyclo‐oxygenases. The antinociceptive characteristics of the combination were evaluated using four different animal models of pain. 2. In the mouse writhing test, antinociceptive properties were observed with ED 50 values of 1.5 ± 0.2 and 120.9 ± 14.8 mg/kg for nefopam and paracetamol, respectively. In the mouse formalin test, both compounds significantly inhibited the licking time of the injected hind paw, with ED 50 values in the early phase of 4.5 ± 1.1 and 330.7 ± 80.3 mg/kg for nefopam and paracetamol, respectively, compared with 4.3 ± 0.2 and 206.1 ± 45.1 mg/kg for nefopam and paracetamol, respectively, in the inflammatory phase. Isobolographic analysis revealed that this drug combination was synergistic in the writhing test and additive in the formalin test. 3. In a rat incision model of postoperative thermal hyperalgesia, coadministration of nefopam at a non‐analgesic dose (3 mg/kg) with paracetamol at a low analgesic dose (300 mg/kg) showed the appearance of a strong antihyperalgesic effect, maintained for at least 3 h. In rat carrageenan‐induced tactile allodynia, the combination of low analgesic doses of nefopam (10 or 30 mg/kg) with a non‐analgesic dose of paracetamol (30 mg/kg), significantly blocked allodynia with a longer duration of efficacy. 4. In conclusion, coadministration of nefopam with paracetamol is worthy of clinical evaluation. 相似文献
15.
The aim of this work was to evaluate the effect of docosahexaenoic acid (DHA) on the pharmacokinetics and pharmacodynamics—nociception—of naproxen in rats, as well as to determine the gastric safety resulting from this combination versus naproxen alone. Female Wistar rats were orally administered DHA, naproxen or the DHA‐naproxen mixture at fixed‐ratio combination of 1:3. The antinociceptive effect was evaluated using the formalin test. The gastric injury was determined 3 h after naproxen administration. An isobolographic analysis was performed to characterize the antinociceptive interaction between DHA and naproxen. To determine the possibility of pharmacokinetic interactions, the oral bioavailability of naproxen was evaluated in presence and absence of oral DHA. The experimental effective dose ED 30 values ( Zexp ) were decreased from theoretical additive dose values ( Zadd ; P < 0.05). The isobolographic analysis showed that the combination exhibited supra‐additive interaction. The oral administration of DHA increased the pharmacokinetic parameter AUC 0‐t of naproxen ( P < 0.05). Furthermore, the gastric damage induced by naproxen was abolished when this drug was combined with DHA. These data suggest that oral administration of DHA‐naproxen combination induces gastric safety and supra‐additive antinociceptive effect in the formalin test so that this combination could be useful to management of inflammatory pain. Drug Dev Res 78 : 332‐339, 2017. © 2017 Wiley Periodicals, Inc. 相似文献
16.
Drug combinations have been used in clinical practice for the main purpose of increasing therapeutic effect efficacy. The aim of this study was to determine the antinociceptive effect of tramadol and caffeine administered separately or in combination, as well as their synergistic interaction. The formalin test was used. Nociceptive behavior was evaluated by flinching response of the formalin-treated paw. Rats were divided into five groups and received tramadol alone (4.9-49.6 mg/kg, s.c.), caffeine alone (1-17.8 mg/kg, p.o.), or combinations of tramadol (4.9, 8.8, 15.6 and 20.8 mg/kg, s.c.) and caffeine (1, 3.16 and 10 mg/kg, p.o.). Tramadol showed dose-dependent antinociceptive effect in both phases of the formalin test. Caffeine only presented antinociceptive effect in the second phase and this effect was also dose-dependent. In Phase 1, combinations of tramadol and caffeine showed antinociceptive effect similar to that of tramadol alone. In Phase 2, the dose-response curve shifted to the left with the combination of tramadol and each dose of caffeine. Synergism analysis resulted in synergistic effect in ten combinations and antagonism in two combinations. In conclusion, the synergism observed in the majority of tramadol and caffeine combinations used in this study suggests that this drug combination is useful in the treatment of pain. 相似文献
17.
Naproxen is an anti‐inflammatory drug used in a variety of anti‐inflammatory syndromes. There is evidence showing that tizanidine enhances the anti‐inflammatory effect in rats. This study examines the pharmacokinetics of naproxen when it is combined with tizanidine. Combining these two drugs is an attractive modality for inflammation complaints. Oral coadministration of naproxen/tizanidine produced a synergistic anti‐inflammatory effect in rats. The swelling of the rat paw was measured by a plethysmometer using carrageenan as an inflammatory agent. In this study, rats received oral doses of naproxen (1, 3, and 4.2 mg/kg), and these doses were combined with a fixed dose of tizanidine (0.01 mg/kg). To evaluate the pharmacokinetic interaction between naproxen/tizanidine, blood samples were obtained at selected times in the 24 h after oral administration and were analyzed using a validated high‐performance liquid chromatography method. Systemic administration of naproxen alone or in combination with tizanidine produced a dose‐dependent anti‐inflammatory effect. In the pharmacokinetic interaction study, no statistically significant difference was observed for the naproxen concentration‐time profiles in the presence of tizanidine. The experimental findings suggest that systemic tizanidine is able to increase the naproxen‐induced anti‐inflammatory effect in rats. This effect was not due to a modification of the bioavailability of naproxen. 相似文献
18.
Ketorolac tromethamine is a nonsteroidal anti‐inflammatory drug (NSAID) effective in the treatment of moderate to severe pain. Tizanidine, an α‐2‐adrenoceptor agonist with myospasmolytic action, is indicated for the treatment of back pain either as monotherapy or in combination with NSAIDs. However, side effects may limit their use. As both drugs produce side effects that are dose dependent, a combination of these drugs appears in order to reduce the dose required for efficacy and, consequently, side effects. In this study, we evaluated the potential synergistic effect of these drugs in the thermal paw stimulation model and their effect on gastric ulcer production in response in the rat. Dose‐response curves for ketorolac and tizanidine were constructed and from these, an ED 40 value was obtained. Isobolographic analysis was carried out based on 0.5:0.5 proportions. In addition, protective effect of tizanidine against ketorolac‐induced gastric damage was evaluated. A synergistic interaction in thermal hyperalgesia and gastroprotective activity was observed, suggesting a good therapeutic potential of this combination in the treatment of pain. 相似文献
19.
The aim of this experimental assay was to assess the antinociceptive interaction between tapentadol and ketorolac in the acetic acid‐induced writhing model in mice. Tapentadol (5.62–31.6 mg/kg ip) or ketorolac (5.62–31.6 mg/kg ip) were administered 15 min before the acetic acid administration. The ED 50 values of the individual drugs were determined and different proportions (tapentadol–ketorolac in 1:1, 3:1, and 1:3) were assayed in combination in the writhing test. Isobolographic analysis and the interaction index demonstrated an antinociceptive synergistic interaction between tapentadol and ketorolac in all combination. Thus, the experimental ED 50 values were lower when compared with their theoretical ED 50 values. These data suggest that the tapentadol–ketorolac combination produces an antinociceptive synergistic interaction in the mouse acetic acid‐induced writhing model. Drug Dev Res 77 : 187–191, 2016. © 2016 Wiley Periodicals, Inc. 相似文献
20.
The purpose of this work was to assess the antinociceptive and antihyperalgesic properties of an herbal preparation, composed of four vegetal species: Pouteria campechiana ( P. campechiana ), Chrysophyllum cainito ( C. cainito ), Citrus limonum ( C. limonum ), and Annona muricata ( A. muricata ), that is commonly used in combination (PCCA) in traditional Mayan medicine for the treatment of diabetes and pain. An ethanolic extract of PCCA was prepared at a ratio of 1:1:1:1 for each plant. The systemic antinociceptive effect of PCCA extract (50–600 mg/kg, p.o.) was dose‐dependent in the rat formalin (1%) producing 66% antinociceptive response at 400 mg/kg, p.o. A concentration‐dependent antinociceptive effect of the PCCA extract (20–160 mg/paw) was also demonstrated in the rat capsaicin (0.2%) test. The PCCA extract (100–400 mg/kg, p.o.) had antihyperalgesic effects in alloxan diabetic rats. These findings demonstrate the antinociceptive and antihyperalgesic effects of PCCA and supports the use of the plant extracts in Mayan folk medicine. Drug Dev Res 78 : 91‐97, 2017. © 2017 Wiley Periodicals, Inc. 相似文献
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