9^th World Congress on Pharmacology September 04-06, 2017 Paris, France

Javier Rejas-Gutiérrez is a Physician, obtained his degree as a General Practitioner at Universidad Complutense of Madrid in 1982 and Doctorate in Public Health at University Rey Juan Carlos (Madrid) in 2003. He completed his Master’s degree in Research Methodology for Health Sciences at Universidad of Barcelona in 2010, an MBA in Pharma Business at EPHOS Business School of Madrid in 1997 and also has Specialist degree in Pharmaceutical Medicine. In his professional career, he worked as a General Practitioner for three years. He has been working in the pharmaceutical industry since 1987 to date in several positions in the field of Clinical Research, Health Economics and Health Outcomes Research. Currently, he is Manager in Health Economics and Outcomes Research (HEOR) department, Market Access & Institutional Relationships Unit at Pfizer Spain.

This post-hoc analysis investigated whether the use of therapeutic doses of pregabalin or gabapentin impact on cost-of-treatment of peripheral neuropathic pain (pNeP) in routine clinical practice. To this end, we analyzed electronic medical records (EMR) of subjects with pNeP followed in primary care centers in Spain. EMR of patients who began treatment with pregabalin (≥150 mgr/day) or gabapentin (≥900 mgr/day) for any health condition causing pNeP during two years within the period lasting from 2008-2012 were included in this analysis and compared with all patients receiving pregabalin or gabapentin irrespectively of doses prescribed. Therapeutic range dose was considered pregabalin 150mg/day or more and gabapentin 900mg/day or more. Health resources utilization and sick leaves along with corresponding costs were computed in year 2015 and compared according with main therapy of pNeP; pregabalin vs. gabapentin. A total of 1163 EMR (pregabalin; N=764, Gabapentin; N=399, 923[79%] within therapeutic range) were analyzed. Mean dose in therapeutic range subgroup were 238.8 (180.1) mgr/day for pregabalin, and 1,210.8 (409.6) mgr/day for gabapentin. Average cost/patient of main medication for pNeP was slightly higher for pregabalin than for gabapentin; 229.2€ vs. 224.2€ (p=0.762) at therapeutic doses, but significantly higher in the whole sample: 214.6€ vs. 157.4€ (p=<0.001). Nonetheless, the average/patient adjusted total cost was lower with pregabalin than with gabapentin; 2,464€ (2,197-2,730) vs. 3,142€ (2,670-3,614), p=0.014 in the therapeutic range analysis, and also in the analysis with the overall sample; 2,413€ (2,119-2,708) vs. 3,201€ (2,806-3,597), p=0.002. These finding may be explained by a significant lower use of concomitant analgesics in the pregabalin subgroup, together with fewer medical visits and days of sick leave. We conclude that treating pNeP with pregabalin is associated with lower-costs in comparison with gabapentin in routine clinical practice in Spain. These findings are observed irrespectively of the range of doses of pregabalin or gabapentin prescribed to patients.

Mike McDonough is a Physician at Footscray Hospital in Melbourne. He specializes in Addiction Medicine & Toxicology. He acts as Chair of the hospital’s ADR committee and has special interest in Medication Safety.

Adverse drug reactions (ADRs) are a common cause of negative health outcomes for patients, often resulting in increase in hospitalization, length of stay and the overall cost. This makes it important to have procedures that minimize risk of inadvertent re-exposure to a drug that has caused the patient an ADR. To evaluate patient receipt and use of ADR warning cards as well as their understanding of ADR information provided, we undertook a retrospective telephone survey of past inpatients who experienced an ADR; this covered the period between January 2013 and April 2016. 82% (89) recalled the ADR event; 55% (49) recalled receiving a temporary ADR warning card and; 73% (65) remember receiving a permanent ADR warning card post-discharge. The ADR warning card was carried by 74% (65) of participants. 85.4% (76) had told their regular GP and 40% (36) had told a pharmacist about their ADR. Overall satisfaction with the current ADR management services was high with 89% (79) agreeing that this adverse drug reaction service was valuable to them. Requiring patients to be responsible for communicating ADRs to all relevant health care professionals outside of this hospital network was not identified as an effective strategy. Patient satisfaction with current ADR management services was high. Many participants still have/use the ADR warning card. Most people were able to participate without reservation.

Mahmoud Alebouyeh has 15 years of experiences in Pharmacology and Pharmacogenetics and is working on gene-base impurities in recombinant therapeutic proteins. He has published 19 articles in scientific journals.

Statement of the Problem: Host cell DNA contamination occurs during the production of biopharmaceuticals and must be controlled and monitored for the purity and safety of the drug products. A dual labeled fluorescent probe Real-Time PCR assay were developed and validated for the quantitative measurement of residual host cell DNA impurity in prokaryote-based (E. coli) recombinant therapeutic proteins which have released in Iranian market. Methodology: In the present study, 48 different types of drugs including insulin, streptokinase, filgrastim, growth hormone and interferon beta 1-b which were available in Iranian market and imported or produced by Iranian companies were examined and the amounts of residual host cell DNA were measured by means of Real-Time PCR. Material & Methods: Real-Time PCR kit purchased and applied according to the manufacturer instructions, real time PCR instrument, micro-centrifuge and 2 mL microfuge tube were used. Following cycling conditions: 10 min at 95â—¦C, one cycle followed by 45 cycles each consisting of 25 s at 95â—¦C, 20 s at 63â—¦C and15 s at 72â—¦C was used. Finding: The mean amount of residual DNA in Iranian manufactured products was 3.54 pg/ml while the amount of residual DNA in imported product was 0.005548 pg/ml which was lower than World Health Organization and U.S. Food and Drug Administration guidelines (10 ng/Dose). Conclusion: The assay was demonstrated to be specific, precise, and accurate to assess residual E. coli DNA in the linear and quantitative range from 1 pg/mL to 100 pg/mL.

Hyun-A Oh completed her BS degree in Biology at Konkuk University in 2013 and currently, she has been working as an integrative course student under the supervision of Dr. Byung Hwa Jung at Korea Institute of Science and Technology (KIST) from March 2013. Her research focuses on “Metabolomics and analytical chemistry using various analytical instruments, such as UPLC-Orbitrap-MS, UPLC-MS/MS, UPLC-TOF-MS, GC-MS and HPLC-UV etc.”

The X decoction, a kind of traditional herb medicines, has been prescribed frequency in the top five for treating asthma, bronchitis, chill and allergic rhinitis for more than hundreds of year in Korea. Nevertheless, no such study has been published yet related to the interaction of X decoction and we need to study for this issue as much as we prescribed. Furthermore, we evaluated activity of natural active compounds by different manufacturer method in X decoction and understood the multi-component interactions, such as herb-herb interaction. The profiling of individual herb and decoction of X decoction was carried out using ultra-high performance liquid chromatography coupled with a quadrupole time of flight mass spectrometry (UPLC-QTOF-MS). Active compounds from X decoction were identified by multivariate analysis and compared activities between two groups. Also, we evaluated anti-inflammatory effect of X decoction investigating the protein expression of iNOS and COX-2 on LPS-induced macrophage RAW 264.7 cells. Chromatogram of individual herbs and decoction of X decoction were detected in positive, negative polarity mode and UV-PDA mode. After multivariate statistical analysis, we found good clustering and many active compounds were identified by comparing fragmentation patterns and plant databases. In this study, activity of active compound related to anti-inflammatory effect was significantly higher in decoction of X decoction than individual herb of X decoction. The result was in accordance with western blot by inhibiting the protein expression of iNOS on LPS-induced macrophage RAW 264.7 cells, in vitro. These results suggest that decoction of X decoction may have anti-inflammatory effect than individual herbs of X decoction.

María Esperanza Avella Vargas is a Professor of Pharmacology and Therapeutics at Military University of Nueva Granada; Leader of the Research Group "Pharmacology, Toxicology and Therapeutics-UMNG" and; responsible for the research seminar "Study of preclinical and clinical research of medicines for its development and application".

Aim: Calea prunifolia H.B.K. (Cp), known as carrasposa has traditionally been used in Colombia as a medicinal plant. The popular use is recommended as arterial hypotensive, antipruritic, antipyretic and antiseborrheic. In the evaluation of the pharmacological profile, promising effects were found in the gastrointestinal system. Materials & Methods: Calea prunifolia H.B.K. extracts, aqueous (EACp) and ethanolic (EECp), administered orally, were evaluated in vivo in groups of six mice. The experimental models used were: Cold stress induced gastric injury, 75% ethanol induced gastric injury, Pyloro ligation and intestinal transit with activated charcoal. The butanolic fraction (FBu) was evaluated in vitro on rat jejunal contractile activity. Results: In cold stress-induced lesions, the number of ulcers cm-2 (mean+standard deviation) presented a significant difference with CPAS at doses (g/kg of weight) of 0.2 (7.7+2.3) and 0.5 (5.5+4.6) in relation to the control (15.2+6.5) and the ILM at the doses of 0.1 (19.5+1.1), 0.2 (15.33+2.2) and 0.5 (13.2+4.5) with control of (30.4+9.1). The EECp showed a significant difference in the number of ulcers and the ILM in the dose of 1g/kg (6.2+4.9) and (16.9+6.0) respectively. In the ethanol-induced lesions, the number of cm-2 ulcers with CPAS at doses of 0.2 (11.7+9.1) and 0.5 (2.0+1.5) had a significant difference in control (36.5+24.5) and ILM at doses of 0.2 24.1+13.0) and 0.5 (10.4+1.9) to the control (53.6+24.8). In pylorus ligation, no treatment group demonstrated significant difference in gastric pH relative to the negative control (water). In intestinal transit with activated charcoal, a significant difference was found in doses of 0.1; 0.2 and 0.5 g/kg EA and at doses of 0.5 EE. In rat jejunal contractile activity, there is significant difference at 37 degrees. Conclusion: EACp and EECp increase the speed of intestinal transit. Direct gastro protective activity is significant, avoiding the formation and decreasing the severity of gastric ulcers induced by stress and ethanol.

Fariba Mohseni has 12 years experiences in adult endocrinology and medical fields and is working on the effects of gene-base impurities in recombinant therapeutic proteins recently. She has published 11 articles in scientific journals.

Statement of the Problem: Chinese hamster ovary (CHO) cells are the host cell for manufacturing of human recombinant proteins drugs in the biopharmaceutical industry. Host cell DNA is an impurity of such manufacturing process and must be controlled and monitored in order to ensure drug purity and safety. Real-time quantitative PCR is a precise method for quantification of residual host cell DNA in therapeutic protein preparations. In the present study, 18 different types of drugs including erythropoietin, interferon beta 1-a, Follicle Stimulating Hormone (FSH), recombinant factor VII which were available in Iranian market and imported or produced by Iranian companies were examined and the amounts of residual host cell DNA were measured by means of real-time PCR. Materials & Methods: Real-time PCR kit purchased and applied according to the manufacturer instructions, real time PCR instrument, micro-centrifuge and 2 mL microfuge tube were used. Following cycling conditions: 10 min at 95◦C, one cycle followed by 50 cycles each consisting of 40 s at 95◦C, 30 s at 60◦C and30 s at 72◦C was used. Results: The mean amount of residual DNA in Iranian manufactured products was 2.14 pg/ml while the amount of residual DNA in imported product was 3.05×10-7 pg/ml which was lower than World Health Organization and U.S. Food and Drug Administration guidelines (10 ng/dose). Discussion: The assay was demonstrated to be specific, precise, and accurate to quantitate residual E. coli DNA in the linear and quantitative range from 1 pg/mL to 100 pg/mL.

Frank Wunder is a senior scientist at Bayer AG in Wuppertal, Germany. His Ph.D. thesis at the Center for Molecular Neurobiology Hamburg (ZMNH) was mainly focussed on the molecular biology of potassium channels. He joined the Bayer pharmaceuticals division in 1993. Wunder has many years of experience in the development of new screening assays, with major focus on cell-based assays for GPCRs, voltage- and ligand-gated ion channels and molecular targets involved in the nitric oxide/cGMP pathway. He has successfully implemented novel screening platforms for cAMP and cGMP. He gained additional expertise in pharmacological models of cardiovascular disease, such as primary cell cultures, isolated heart preparations, and in vivo models.

Corin is a transmembrane serine protease expressed in cardiomyocytes. Single Nucleotide Polymorphisms (SNPs) and mutations in the Corin gene leading to reduced corin activity were identified in patients with hypertension, cardiac hypertrophy and heart failure. Corin exerts its cardio protective effects via the proteolytic cleavage and activation of pro-atrial natriuretic peptide (pro-ANP) to ANP. Binding of mature ANP to the ANP receptor (GC-A) augments intracellular cGMP levels in target organs such as kidneys and peripheral blood vessels, ultimately leading to reduced blood volume and pressure. We recently described a reporter cell line stably expressing both the receptor guanylyl cyclase GC-A and the cGMP-dependent cation channel CNGA2, which was used as a real-time cGMP biosensor. Additional expression of the Ca2+-sensitive photoprotein aequorin allowed natriuretic peptide detection by luminescence measurements. However, upon ANP stimulation luminescent signals were found to be transient. Therefore, we generated a second reporter cell line which expressed the calcium-sensitive GFP variant GCaMP6 instead of aequorin. In contrast to the luminescence-based reporter cell line, ANP stimulation of our novel GCAMP6 reporter cell resulted in stable, long-lasting fluorescence signals. Using this reporter system, we could show that recombinant soluble wild type corin (solCorin), but not the active site mutant corin (S985A) is able to convert proANP to ANP, resulting in left-shifted concentration-response curves. Equally, the cardiomyocyte derived HL-1 cell line converted proANP to ANP while HL-1 corin knockout cells did not. Furthermore, transient overexpression of corin conferred proANPase activity to HEK293 cells. Our findings underline the role of corin as the proANPase. The fluorescence-based ANP reporter cell line is well-suited for the characterization of corin modulators, structure-function studies of corin variants, and might be used for the identification of novel corin activators by HTS.

Bing-Chang Chen completed his Graduation in Department of Pharmacy at Chia-Nan Junior College of Pharmacy in 1991 and; PhD at Institute of Pharmacology, College of Medicine, National Taiwan University (NTU), Taiwan in 1999. He completed his Post-doctoral training at Institute of Pharmacology, College of Medicine, NTU from 1999-2001. Currently, he is a Director of Master program of School of Respiratory Therapy at Taipei Medical University (TMU) and also a member of Lung Inflammation Research Group (LIRG) in TMU. His research interests include “Molecular mechanisms of thrombin in chemokine IL-8/CXCL8 expression and lung inflammation; signaling transduction of ADAM17 in pulmonary fibrosis of chronic obstructive asthma (COA) and; pharmacology in respiratory diseases”.

Thrombin plays an important role in lung inflammatory diseases such as asthma. Several studies have shown that thrombin can induce interleukin-8 (IL-8)/CXCL8 in lung epithelial cells, and it plays a critical role in lung inflammation. We previously showed that thrombin induces IL-8/CXCL8 expression via the c-Src- and Rac1/PI3K/Akt-dependent IB kinase / (IKK/)/NF-B signaling pathways in human lung epithelial cells. In this study, we further investigated the roles of mammalian target of rapamycin (mTOR), p70S6K, p300, and NF-B in thrombin-induced IL-8/CXCL8 expression in human lung epithelial cells. Thrombin-induced IL-8/CXCL8 release was attenuated by rapamycin (a mTOR inhibitor), p70S6K siRNA, and p300 siRNA. Treatment of cells with thrombin caused a time-dependent increase in phosphorylation of mTOR at Ser2448, p70S6K at Thr389, and p300 at Ser1834. Thrombin-induced an increase in p70S6K phosphorylation was inhibited by rapamycin. Thrombin-induced an increase in p300 phosphorylation was inhibited by rapamycin and p70S6K siRNA. Moreover, thrombin-induced phosphorylations of mTOR, p70S6K, and p300 were inhibited by dominant negative mutant of Akt (AktDN). Thrombin caused p70S6K translocation from the cytosol to the nucleus in a time-dependent manner. Treatment of cells with thrombin induced p70S6K, p300, and p65 complex formation. Thrombin caused time-dependent increase p65 Lys310 acetylation and the recruitment of p300 and p65 to the IL-8/CXCL8 promoter. These results indicated that thrombin activates mTOR/p70S6K/p300 signaling pathway to induce NF-B activation and IL-8/CXCL8 expression in human lung epithelial cells.

Bernadette Lázár is a PhD student at Semmelweis University, where she participates in pharmacological analysis of gastrointestinal functions in rodents by using in vivo, ex vivo and in vitro methods. The aim is to characterize the COX-2 inhibitor effects at the gastrointestinal tract, and to reveal the causes and consequences of the gut flora composition change.

Introduction & Aim: It is well known that NSAIDs, which are among the most commonly used drugs worldwide, may cause gastric and duodenal ulceration, but in recent years it has been found that the distal parts of the small intestine are also injured. The patho-mechanism of this enteropathy is complex and insufficiently understood. Based on the literature, the inhibition of cyclooxygenase (COX) -1 enzyme and the acidic character of the compounds both play a role in the damage of intestinal mucosa, but it still remains controversial whether the selective inhibition of COX-2 enzyme can induce enteropathy. Thus, in our present experiment, the aim was to characterize the effects of chronic, selective COX-2 inhibition in the gastrointestinal tract. Methods: Male Wistar rats (180-200 g) were treated for 1 month with either the selective, non-acidic COX-2 inhibitor rofecoxib (5 mg/kg per day, once daily) or with its vehicle (1% methylcellulose). Gastric and intestinal mucosal injury was assessed by macroscopic and histological methods. The microbial composition of the small intestinal contents was investigated by 16S rRNA Illumina sequencing, and the effect of rofecoxib on the growth of bacteria was examined by micro dilution assay. Results: The 1-month rofecoxib treatment did not alter the body weight of the animals and did not cause significant macroscopic or histological injury in the stomach and small intestine. However, our results indicate that although rofecoxib has no direct antibacterial property, it caused significant changes in the small intestinal microbiota. Conclusion: Based on our results, selective COX-2 enzyme inhibition, even chronically, does not cause mucosal damage in the stomach or in the small intestine, but it significantly changes the gut flora composition. Our further studies will aim to reveal the cause and consequences of this dysbiosis.

Matheus L Rocha completed his Graduation in Pharmaceutical Sciences at Universidade Metodista de Piracicaba/SP (2001); Master's degree in Physiology at Universidade Federal de São Carlos (2004) and; PhD in Pharmacology at Universidade de São Paulo (2007). He holds a Post-doctoral degree in Pharmacology at Medical School of São Paulo University. He has experience in Pharmacy and Medical Sciences, focusing on cardiovascular, pharmacology and physiology, acting on the following subjects: Ca2+ availability, isolated arterial beds (contraction and relaxation), myocardium contraction and medicinal natural products.

Statement of the Problem: Jabuticaba is an exotic fruit native to Brazil that has been arousing medicinal interest. Despite the important biological effects, its actions on the cardiovascular system remain untested. Thus, hydro-alcoholic extract of jabuticaba (HEJ) could improve the cardiovascular damages caused by hypertension. Methodology & Theoretical Orientation: Hypertension was induced in rats by oral administration with L-NAME (60 mg/Kg/day in drinking water) for six weeks. HEJ was administered orally (100 or 300 mg/Kg/day by gavage) starting at the second week along with oral treatment with L-NAME. The blood pressure and heart rate were recorded weekly by tail-cuff plethysmography. After six weeks, the rats were sacrificed and the heart and left kidney were weighted. Aortas were isolated and set up to isometric recordings in an organ bath to verify the capacity of contraction and relaxation. The capacity of HEJ induce nitric oxide production in endothelial cells was analyzed by flow cytometry. Moreover, the phytochemistry composition and antioxidant potential of HEJ were analyzed by HPLC, mass spectrometry and differential pulse voltammetry. Findings: Our phytochemistry and antioxidant results have shown the presence of phenolic compounds and high antioxidant capacity to HEJ. The arterial hypertension (225.8±11.2 mmHg) was reduced after HEJ 100 e 300 mg/kg/day treatment (163.4±8.7 e 172.1±9.3 mmHg, respectively). The heart and kidney weight from hypertensive rats were reduced. The vascular relaxation to acetylcholine and sodium nitroprusside and the contraction induced by phenylephrine were impaired in hypertensive group. The treatment with either 100 or 300 mg/Kg HEJ significantly improved the vascular response for these agents. HEJ was able to induce NO release from endothelial cells. Conclusion & Significance: HEJ presents high antioxidant potential. The treatment with HEJ attenuated hypertension possibly improving the NO biodisponibility. The relaxation endothelium-dependent and independent was impaired by hypertension and improved after treatment with HEJ.

Nacira Benahmed contributes to one of the scientific researches in the laboratory of phytochemical and organic synthesis (LPSO) which is based on the study of the inhibitory power of extracts of medicinal plants of the region of the south west of Algeria on crystallisation of phosphates lithiasis.

The urolithiasis constitutes a major problem to public health. It is a disease resulting from the presence of stones in the kidneys or urinary tract. It, increasingly every day, asserts itself as a sign which reflects our socio-economic life conditions, and our dietary habits. Many plants species, described in pharmacopoeias of several countries is used as a remedy for urinary stones. The selection of the plant Ziziphus lotus (Rhamnaceae family) was done according to an ethnopharmacological survey on medicinal plants used in the region of the south west of Algeria to cure the urinary tract diseases. On the first stage, we have studied the crystallization of struvite “in vitro” without inhibitors. The work was resumed, and this time by crystallization with inhibitors in order to explore the influence of the medicinal plant extracts on the phase of crystallization of struvite. We have used an optical polarizing microscope to follow the evolution of the size of crystals and aggregates as a function of time. At the end of the experiment, the crystallization precipitate subjected to the spectroscopic analysis IRTF. The results of the most of the organic and aqueous extracts compared to crystallization without inhibitor have a significant inhibitory effect on the size of crystals and aggregates of struvite. It is very important reduction for the aqueous, chloroforme and hexane extracts (12 to 5-8μm), we have observed a decrease in the size of the aggregates in the presence of all the extracts. This reduction is important for the chloroforme extract (45 to 8-10 μm) and hexanes extract (45 to 8-12 μm)

María Esperanza Avella Vargas is a Professor of Pharmacology and Therapeutics at Military University of Nueva Granada; Leader of the Research Group "Pharmacology, Toxicology and Therapeutics-UMNG" and; responsible for the research seminar "Study of preclinical and clinical research of medicines for its development and application".

Purpose: Calea prunifolia H.B.K. (Cp), known as "carrasposa" has traditionally been used in Colombia as a medicinal plant. Th e popular use is recommended as arterial hypotensive, antipruritic, antipyretic and antiseborreic. As part of the knowledge of its pharmacological profi le, its eff ects on the central nervous system and as analgesic and anti-infl ammatory were studied. Materials and Methods: Th e extracts, aqueous (EACp), ethanolic (EPAp) and the Butanolic Fraction (FBu) of Calea prunifolia H.B.K., orally administered, were evaluated in vivo in albino Swiss adult mice. To study the eff ect on the central nervous system, the following tests were performed: Motor coordination test, Rota-Rod test, Evaluation of the Exploratory Activity: Open fi eld test, Evaluation of hypnosis activity, Sleep induced by barbiturate and evaluation of body temperature. Th e evaluation of antinociceptive activity with the formaldehyde test, Tail-fl ick test and evaluation of analgesic activity, with the test of abdominal contortions induced by acetic acid. Proof of anti-infl ammatory activity in the paw edema test and the carrageenan-induced peritonitis test. Results: In the motor performance test (Rota Rod), the latency for the fi rst drop and the residence time of the animals showed no diff erence between the treatments and the control, nor were there changes in body temperature. In the evaluation of the exploratory Activity, the EECp showed a signifi cant diff erence (p <0.05) in relation to the control, with greater number of crossings and the mobility time, both in the periphery and in the center of the fi eld at doses of 0.1, 0.3 and 1 g / kg p.o. and FBu at the dose of 1 g / kg p.o. In the evaluation of the hypnosing activity, with the sleep test induced by pentobarbital (50mg / kg i.p.), a signifi cant increase (p <0.05) in the latency time was observed in all doses of FBu (0.1, 0.3 and 1 g / kg p.o.) and the highest dose of the EECp 1g / kg. A signifi cant analgesic eff ect (p <0.05) like indomethacin was observed in the 1.5% formaldehyde test (30 μL / paw, s.p.), with the EACp and EECp at the highest concentration (1 g / Kg p.o.) relative to the control. In the Tail-fl ick test, there is a protective eff ect at 30 min of administration of the EACp at the dose of 0.5 mg / kg and a signifi cant antinociceptive eff ect (p <0.01) in the test of abdominal contortions induced by 0.8% acetic acid in mice, with administration of EACp (0.1, 0.2 and 0.5 g / kg p.o.). No anti-infl ammatory eff ect was demonstrated in the tests used. Conclusion: In these screening tests, Cp presents analgesic eff ects that must be evaluated and confi rmed in the determination of its mechanisms of action, as a potential pharmacological resource for pain management.