M. Strozik, M. Strzebońska, Katarzyna Skiba, Wiktor Tatara
Bromhexine hydrochloride (BRX) is widely applied as an active pharmaceutical ingredient of oral solutions and tablets for the treatment of the infections of the respiratory tract. However, fulfillment of the present regulations, required for the registration process of BRX, might constitute a challenge, due to the occurrence of (3RS)-6,8-dibromo-3-cyclohexyl-3-methyl-1,2,3,4-tetrahydroquinazolin-3-ium, specified as impurity E by European Pharmacopeia. To overcome this issue, a novel BRX orodispersible tablets (ODT) with improved chemical stability were developed that contain low level of impurity E. Herein the analytical methods, elaborated for the determination of BRX and the related impurities in this product are presented. Stability of the product was tested at accelerated (ACC), intermediate (INT) and long-term (LT) conditions for ICH zones II and III. The degradant E was the most common impurity detected. In the samples stored in INT and LT conditions only a slight increase in the impurities and a slight drop in the assay of the BRX was observed, however the results did not exceed the pre-established acceptance criteria. In the samples stored at ACC conditions, an increase of the known impurities, including degradant E, degradant B and N-oxide, was noted. Noteworthily, even after three years of the product’s shelf-life, the level of the degradant E is still below 0.2 % which corresponds to the ICH identification threshold for the BRX related impurities.
{"title":"Development and validation of the analytical methods for determination of bromhexine hydrochloride and related impurities in novel orodispersible tablets","authors":"M. Strozik, M. Strzebońska, Katarzyna Skiba, Wiktor Tatara","doi":"10.32383/appdr/152632","DOIUrl":"https://doi.org/10.32383/appdr/152632","url":null,"abstract":"Bromhexine hydrochloride (BRX) is widely applied as an active pharmaceutical ingredient of oral solutions and tablets for the treatment of the infections of the respiratory tract. However, fulfillment of the present regulations, required for the registration process of BRX, might constitute a challenge, due to the occurrence of (3RS)-6,8-dibromo-3-cyclohexyl-3-methyl-1,2,3,4-tetrahydroquinazolin-3-ium, specified as impurity E by European Pharmacopeia. To overcome this issue, a novel BRX orodispersible tablets (ODT) with improved chemical stability were developed that contain low level of impurity E. Herein the analytical methods, elaborated for the determination of BRX and the related impurities in this product are presented. Stability of the product was tested at accelerated (ACC), intermediate (INT) and long-term (LT) conditions for ICH zones II and III. The degradant E was the most common impurity detected. In the samples stored in INT and LT conditions only a slight increase in the impurities and a slight drop in the assay of the BRX was observed, however the results did not exceed the pre-established acceptance criteria. In the samples stored at ACC conditions, an increase of the known impurities, including degradant E, degradant B and N-oxide, was noted. Noteworthily, even after three years of the product’s shelf-life, the level of the degradant E is still below 0.2 % which corresponds to the ICH identification threshold for the BRX related impurities.","PeriodicalId":7147,"journal":{"name":"Acta poloniae pharmaceutica","volume":" ","pages":""},"PeriodicalIF":0.4,"publicationDate":"2022-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42882239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Skeletal muscle (SM) is a most complex and plastic tissues of the human body. Movement, postural support, breathing, and thermogenesis are important functions of SM. Muscle mass reduction is a common side effect of human aging. The growth factor myostatin (MSTN) appears to play a key role in aging-related muscle function decreases. Targeting MSTN might help people live longer by preventing SM alterations associated with aging. Therefore, in the present study, FDA-approved drugs (from 2015 to 2020, total 273 drugs) were screened against MSTN to find the best drugs against MSTN for the management of aging disease. In this regards, Screening, docking, and molecular dynamics simulation was used. Based on structure-based virtual screening and free energy of bind, we select the top five drugs as mentioned in this article. Two drugs were analyzed in-depth namely, Sonidegib and Revefenacin showing free energy of binding -10.95 and -12.03 kcal/mol respectively with MSTN. Further, these complex was forwarded for molecular dynamics simulation to check the structural stability during 100ns, which was found to be more stable. As a concluding remark, Sonidegib and Revefenacin can be considered for further designing of new drugs against MSTN for the treatment aging related disorders.
{"title":"An insight of FDA-approved drugs for the management of aging related disorder a in silico study","authors":"Tong-jie Yang, Quan Wan, PENG-PENG Wen","doi":"10.32383/appdr/152839","DOIUrl":"https://doi.org/10.32383/appdr/152839","url":null,"abstract":"Skeletal muscle (SM) is a most complex and plastic tissues of the human body. Movement, postural support, breathing, and thermogenesis are important functions of SM. Muscle mass reduction is a common side effect of human aging. The growth factor myostatin (MSTN) appears to play a key role in aging-related muscle function decreases. Targeting MSTN might help people live longer by preventing SM alterations associated with aging. Therefore, in the present study, FDA-approved drugs (from 2015 to 2020, total 273 drugs) were screened against MSTN to find the best drugs against MSTN for the management of aging disease. In this regards, Screening, docking, and molecular dynamics simulation was used. Based on structure-based virtual screening and free energy of bind, we select the top five drugs as mentioned in this article. Two drugs were analyzed in-depth namely, Sonidegib and Revefenacin showing free energy of binding -10.95 and -12.03 kcal/mol respectively with MSTN. Further, these complex was forwarded for molecular dynamics simulation to check the structural stability during 100ns, which was found to be more stable. As a concluding remark, Sonidegib and Revefenacin can be considered for further designing of new drugs against MSTN for the treatment aging related disorders.","PeriodicalId":7147,"journal":{"name":"Acta poloniae pharmaceutica","volume":" ","pages":""},"PeriodicalIF":0.4,"publicationDate":"2022-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45909256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. Koç, U. Kuyrukluyıldız, Ali Caner Sayar, Mustafa Gazi, B. Süleyman, R. Mammadov, Nergis Akbaş, R. Arslan, H. Suleyman, Bulent Yavuzer
Long-term treatment with tramadol is reported to be toxic to the kidneys. Research shows that tramadol reduces antioxidants and increases oxidants produced in renal tissue. This study aims to investigate the carvacrol effect on tramadol-induced renal injury in rats. The animals were divided into four groups: healthy (HG), individual tramadol (TR), individual carvacrol (CR), and tramadol + carvacrol (TC). Malondialdehyde (MDA), total glutathione (tGSH), glutathione peroxidase (GPO), superoxide dismutase (SOD), total oxidant status (TOS), total antioxidant status (TAS), blood urea nitrogen (BUN), and creatinine (Cr) were measured. Renal tissue was examined histopathologically. MDA, TOS, BUN, and Cr were significantly elevated in group TR and identified as low in group TC compared to group TR but higher than in the HG group. The tGSH, SOD, GPO, and TAS levels were low in group TR and higher in group TC than in group TR but lower than in the HG group. Histological examination of the TR group revealed diffuse necrosis and focal polymorphonuclear leukocytes (PMNLs) in the tubules. In the TC group, tubular atrophy and necrosis were minimal, and PMNL was rare. We observed that tramadol increases oxidants, decreases antioxidants, increases BUN and Cr, and examined whether the toxic effect on renal tissue regressed with carvacrol.
{"title":"The effect of carvacrol on tramadol-induced oxidative renal injury in rats: biochemical and histopathological evaluation","authors":"A. Koç, U. Kuyrukluyıldız, Ali Caner Sayar, Mustafa Gazi, B. Süleyman, R. Mammadov, Nergis Akbaş, R. Arslan, H. Suleyman, Bulent Yavuzer","doi":"10.32383/appdr/154638","DOIUrl":"https://doi.org/10.32383/appdr/154638","url":null,"abstract":"Long-term treatment with tramadol is reported to be toxic to the kidneys. Research shows that tramadol reduces antioxidants and increases oxidants produced in renal tissue. This study aims to investigate the carvacrol effect on tramadol-induced renal injury in rats. The animals were divided into four groups: healthy (HG), individual tramadol (TR), individual carvacrol (CR), and tramadol + carvacrol (TC). Malondialdehyde (MDA), total glutathione (tGSH), glutathione peroxidase (GPO), superoxide dismutase (SOD), total oxidant status (TOS), total antioxidant status (TAS), blood urea nitrogen (BUN), and creatinine (Cr) were measured. Renal tissue was examined histopathologically. MDA, TOS, BUN, and Cr were significantly elevated in group TR and identified as low in group TC compared to group TR but higher than in the HG group. The tGSH, SOD, GPO, and TAS levels were low in group TR and higher in group TC than in group TR but lower than in the HG group. Histological examination of the TR group revealed diffuse necrosis and focal polymorphonuclear leukocytes (PMNLs) in the tubules. In the TC group, tubular atrophy and necrosis were minimal, and PMNL was rare. We observed that tramadol increases oxidants, decreases antioxidants, increases BUN and Cr, and examined whether the toxic effect on renal tissue regressed with carvacrol.","PeriodicalId":7147,"journal":{"name":"Acta poloniae pharmaceutica","volume":" ","pages":""},"PeriodicalIF":0.4,"publicationDate":"2022-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47177519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Practising the profession of a doctor involves high social recognition but also entails responsibility for the health and life of a patient. In this context, pharmacological treatment applied in compliance with the formal registration of a medicinal product does not raise any serious concerns. However, it is not always possible to administer a medicine in a way that corresponds to its official characteristics. Clinical practice shows that it is often necessary to administer a medicine outside the requirements specified in the summary of product characteristics. In such cases, a legal, ethical and typically medical problem arises. The aim of the study is to analyse the entire legal environment of the doctors’ use of medicines outside the summary of product characteristics. The discussion leads to the conclusion that medical personnel are fully authorised to administer a medicinal product outside its official characteristics. However, this may only take place if such a decision is based on current knowledge, the doctor’s individual experience and acting in the best interest of the patient, as well as proper diagnosis of his/her current therapeutic needs. The legal regulations in force in Poland are sufficient in that sphere to ensure the well-being of the patient and protect the interests of the doctor, although – it should be admitted – their wording is not unambiguous enough to prevent more or less serious doubts as to their interpretation. Hence the proposal for legal clarification of the situation related to the administration of a medicine off-label.
{"title":"Permissibility of the off-label use of a medicinal product in the context of a doctor’s liability – an attempt at clarification of the issue under the Polish law","authors":"Krzysztof Kozłowski, W. Wierzba, B. Machaliński","doi":"10.32383/appdr/153591","DOIUrl":"https://doi.org/10.32383/appdr/153591","url":null,"abstract":"Practising the profession of a doctor involves high social recognition but also entails responsibility for the health and life of a patient. In this context, pharmacological treatment applied in compliance with the formal registration of a medicinal product does not raise any serious concerns. However, it is not always possible to administer a medicine in a way that corresponds to its official characteristics. Clinical practice shows that it is often necessary to administer a medicine outside the requirements specified in the summary of product characteristics. In such cases, a legal, ethical and typically medical problem arises. The aim of the study is to analyse the entire legal environment of the doctors’ use of medicines outside the summary of product characteristics. The discussion leads to the conclusion that medical personnel are fully authorised to administer a medicinal product outside its official characteristics. However, this may only take place if such a decision is based on current knowledge, the doctor’s individual experience and acting in the best interest of the patient, as well as proper diagnosis of his/her current therapeutic needs. The legal regulations in force in Poland are sufficient in that sphere to ensure the well-being of the patient and protect the interests of the doctor, although – it should be admitted – their wording is not unambiguous enough to prevent more or less serious doubts as to their interpretation. Hence the proposal for legal clarification of the situation related to the administration of a medicine off-label.","PeriodicalId":7147,"journal":{"name":"Acta poloniae pharmaceutica","volume":" ","pages":""},"PeriodicalIF":0.4,"publicationDate":"2022-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47824385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Valproic acid and its derivatives are drugs that have been used in many neurogenic diseases, but are mainly used in epileptic seizures. Due to the fact that valproic acid doesn’t have conjugated double bonds, it isn’t visible under UV light and its detection is difficult. Therefore, the aim of the study was to assess the suitability of individual visualizing reagents in the chemical qualitative and quantitative detection of valproic acid using the TLC technique. Solutions of various visualizing reagents were prepared, and then the reagents were applied on the previously prepared chromatographic plates with valproic acid by means of an immersion and spraying method in order to detect it. It was shown that all the visualizing reagents used, with the exception of helasol green, bromothymol blue, malachite green, bromocresol green in 2% sodium hydroxide solution and sulphate (VI) solutions of iron (II), nickel and cobalt, allowed for the qualitative detection of valproic acid. It is recommended to use a 1% solution of copper (II) sulphate (VI) for the detection of valproic acid for both qualitative and quantitative purposes, due to the largest areas of the chromatographic bands on most of the chromatographic plates used in the study. There is a potential possibility of examining the identity of valproic acid present in drugs on the basis of the RF value, the characteristic colour of the spot, and a comparative analysis of spectrodensitograms.
{"title":"TLC-densitometric identification of valproic acid","authors":"Wioletta Parys, A. Pyka","doi":"10.32383/appdr/152702","DOIUrl":"https://doi.org/10.32383/appdr/152702","url":null,"abstract":"Valproic acid and its derivatives are drugs that have been used in many neurogenic diseases, but are mainly used in epileptic seizures. Due to the fact that valproic acid doesn’t have conjugated double bonds, it isn’t visible under UV light and its detection is difficult. Therefore, the aim of the study was to assess the suitability of individual visualizing reagents in the chemical qualitative and quantitative detection of valproic acid using the TLC technique. Solutions of various visualizing reagents were prepared, and then the reagents were applied on the previously prepared chromatographic plates with valproic acid by means of an immersion and spraying method in order to detect it. It was shown that all the visualizing reagents used, with the exception of helasol green, bromothymol blue, malachite green, bromocresol green in 2% sodium hydroxide solution and sulphate (VI) solutions of iron (II), nickel and cobalt, allowed for the qualitative detection of valproic acid. It is recommended to use a 1% solution of copper (II) sulphate (VI) for the detection of valproic acid for both qualitative and quantitative purposes, due to the largest areas of the chromatographic bands on most of the chromatographic plates used in the study. There is a potential possibility of examining the identity of valproic acid present in drugs on the basis of the RF value, the characteristic colour of the spot, and a comparative analysis of spectrodensitograms.","PeriodicalId":7147,"journal":{"name":"Acta poloniae pharmaceutica","volume":" ","pages":""},"PeriodicalIF":0.4,"publicationDate":"2022-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48521329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
T. Guszczyn, Magda Chalecka, Adam Kazberuk, Ilona Ościłowska, J. Pałka, A. Surazynski
Although inflammation is the first step in wound healing, it contributes to down-regulation of collagen biosynthesis delaying the process of tissue regeneration. The study was conducted to evaluate the effects of platelet-rich plasma (PRP) on interleukin-1β (IL-1β) – dependent inhibition of collagen synthesis, prolidase activity, and β1-integrin signaling in cultured human skin fibroblasts. PRP was obtain using the SmartPReP®2 Autologous Platelet Concentrate+ System. Collagen biosynthesis and prolidase activity were measured in confluent human skin fibroblast cultures with IL-1β, PRP, hyaluronic acid (HA), and mixtures of IL-1β with PRP or HA. Immunofluorescence bioimaging analysis was employed to evaluate expression of β1 integrin receptor, cyclooxygenase-2 (COX-2) and nuclear factor-κB (NF-κB) protein. Incubation of fibroblasts with 2% PRP for 24 h contributed to about 500% increase in collagen biosynthesis and a significant increase in the expression of β1-integrin receptor and prolidase activity, compared to the control cells. In the cells treated with IL-1β, collagen biosynthesis, β1-integrin receptor expression, and prolidase activity were decreased while COX-2 and NF-κB expressions were significantly increased. All these processes were recovered to control values by PRP or HA; however, PRP was found to act more effectively than HA. It was found that PRP counteracted IL-1β -dependent inhibition of collagen synthesis through recovery of β1-integrin receptor expression and prolidase activity and down-regulation of COX-2 and NF-κB expressions in cultured fibroblasts. The data suggest that PRP evoke anti-inflammatory activity that is desirable in tissue regeneration.
{"title":"Platelet-rich plasma counteracts interleukin-1 induced inhibition of collagen biosynthesis through recovery of impaired β1-integrin signaling and prolidase activity in human skin fibroblasts.","authors":"T. Guszczyn, Magda Chalecka, Adam Kazberuk, Ilona Ościłowska, J. Pałka, A. Surazynski","doi":"10.32383/appdr/154045","DOIUrl":"https://doi.org/10.32383/appdr/154045","url":null,"abstract":"Although inflammation is the first step in wound healing, it contributes to down-regulation of collagen biosynthesis delaying the process of tissue regeneration. The study was conducted to evaluate the effects of platelet-rich plasma (PRP) on interleukin-1β (IL-1β) – dependent inhibition of collagen synthesis, prolidase activity, and β1-integrin signaling in cultured human skin fibroblasts. PRP was obtain using the SmartPReP®2 Autologous Platelet Concentrate+ System. Collagen biosynthesis and prolidase activity were measured in confluent human skin fibroblast cultures with IL-1β, PRP, hyaluronic acid (HA), and mixtures of IL-1β with PRP or HA. Immunofluorescence bioimaging analysis was employed to evaluate expression of β1 integrin receptor, cyclooxygenase-2 (COX-2) and nuclear factor-κB (NF-κB) protein. Incubation of fibroblasts with 2% PRP for 24 h contributed to about 500% increase in collagen biosynthesis and a significant increase in the expression of β1-integrin receptor and prolidase activity, compared to the control cells. In the cells treated with IL-1β, collagen biosynthesis, β1-integrin receptor expression, and prolidase activity were decreased while COX-2 and NF-κB expressions were significantly increased. All these processes were recovered to control values by PRP or HA; however, PRP was found to act more effectively than HA. It was found that PRP counteracted IL-1β -dependent inhibition of collagen synthesis through recovery of β1-integrin receptor expression and prolidase activity and down-regulation of COX-2 and NF-κB expressions in cultured fibroblasts. The data suggest that PRP evoke anti-inflammatory activity that is desirable in tissue regeneration.","PeriodicalId":7147,"journal":{"name":"Acta poloniae pharmaceutica","volume":" ","pages":""},"PeriodicalIF":0.4,"publicationDate":"2022-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47284233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
L. Bułaś, Beata Szulc - Musioł, Wioletta Siemiradzka, Małgorzata Służalec, B. Dolińska
Abstract: The study evaluated the release of salicylic acid with new two multiphase ointment bases: Fitalite™ and Nourivan™ Antiox. Fitalite™ is a cream-gel base while Nourivan™ Antiox is a cream oil in water. Salicylic acid is a substance often used in the formulation of semi-solid dosage forms applied on the skin. The release rate of salicylic acid was examined depending on the base and the particle size of the active ingredient. For this purpose, formulations containing 5% salicylic acid were prepared and used for the study. Three different methods were used for the incorporation of salicylic acid into the bases: non-grinded, ground with the base for 15 minutes, and concentrate of salicylic acid with white soft paraffin (1:1). Measurements of the particles of the active substance in each of the preparations were also taken. Salicylic acid has been shown to be released to a greater extent from Fitalite ™ base. Qualitative analysis of the composition of the bases, in studies conducted by the Department staff, allows concluding that the amount and release rate of salicylic acid from the bases is influenced by its viscosity. This parameter has a significant impact on the level of trituration of salicylic acid. It was also found that the concentrate of salicylic acid with white soft paraffin (1:1) reduces the time of preparation of a suspension type ointment with salicylic acid, wherein the particle size accomplishes the requirements of pharmacopeia.
{"title":"Release of salicylic acid from new multiphase bases with consideration of the preparation method","authors":"L. Bułaś, Beata Szulc - Musioł, Wioletta Siemiradzka, Małgorzata Służalec, B. Dolińska","doi":"10.32383/appdr/154891","DOIUrl":"https://doi.org/10.32383/appdr/154891","url":null,"abstract":"Abstract: The study evaluated the release of salicylic acid with new two multiphase ointment bases: Fitalite™ and Nourivan™ Antiox. Fitalite™ is a cream-gel base while Nourivan™ Antiox is a cream oil in water. Salicylic acid is a substance often used in the formulation of semi-solid dosage forms applied on the skin. The release rate of salicylic acid was examined depending on the base and the particle size of the active ingredient. For this purpose, formulations containing 5% salicylic acid were prepared and used for the study. Three different methods were used for the incorporation of salicylic acid into the bases: non-grinded, ground with the base for 15 minutes, and concentrate of salicylic acid with white soft paraffin (1:1). Measurements of the particles of the active substance in each of the preparations were also taken. Salicylic acid has been shown to be released to a greater extent from Fitalite ™ base. Qualitative analysis of the composition of the bases, in studies conducted by the Department staff, allows concluding that the amount and release rate of salicylic acid from the bases is influenced by its viscosity. This parameter has a significant impact on the level of trituration of salicylic acid. It was also found that the concentrate of salicylic acid with white soft paraffin (1:1) reduces the time of preparation of a suspension type ointment with salicylic acid, wherein the particle size accomplishes the requirements of pharmacopeia.","PeriodicalId":7147,"journal":{"name":"Acta poloniae pharmaceutica","volume":" ","pages":""},"PeriodicalIF":0.4,"publicationDate":"2022-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42695033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ceren Kaya, Nazlı Turan Yücel, Ümmühan Kandemir, Derya Osmaniye, Ö. Can, Ümide Demir Özkay
It was aimed to synthesize some novel piperidine derivatives and investigate their antidepressant-like activities, in this study. Targeted compounds were obtained by reacting 1-(4-(substitutedpiperidin-1-yl)phenyl)ethan-1-one and heterocyclic aldehydes in methanol. The structures of the synthesized compounds were determined using data from various spectroscopic methods (IR, 1H-NMR, 13C-NMR, and LCMSMS). The compounds (50 mg/kg) were tested for their antidepressant-like effects by tail suspension and modified forced swimming tests (MFST). In addition, possible alterations in locomotor activities of mice were evaluated by activity cage measurements. Obtained results showed that compounds 2c-2f reduced the immobility time of mice in both of the antidepressant activity-screening tests indicating that these derivatives have antidepressant-like effects. Moreover, in MFST, compounds 2c and 2e significantly increased the swimming times, while compounds 2d and 2f significantly prolonged the climbing durations. Antidepressant-like effects of the compounds 2c and 2e was reversed with p-chlorophenylalanine methyl ester (serotonin depleting agent) pre-treatments while the same effect caused by the compounds 2d and 2f was abolished by pretreatment with α-methyl-para-tyrosine methyl ester (catecholamine depleting agent) pre-administrations. Moreover, pre-treatment with naloxone reversed the antidepressant-like effects of these four derivatives. Obtained results indicated that monoaminergic and opioidergic systems mediated the antidepressant-like effects of our novel piperidine derivatives.
{"title":"Synthesis and antidepressant-like activities of some piperidine derivatives: \u0000involvements of monoaminergic and opiodergic systems","authors":"Ceren Kaya, Nazlı Turan Yücel, Ümmühan Kandemir, Derya Osmaniye, Ö. Can, Ümide Demir Özkay","doi":"10.32383/appdr/152631","DOIUrl":"https://doi.org/10.32383/appdr/152631","url":null,"abstract":"It was aimed to synthesize some novel piperidine derivatives and investigate their antidepressant-like activities, in this study. Targeted compounds were obtained by reacting 1-(4-(substitutedpiperidin-1-yl)phenyl)ethan-1-one and heterocyclic aldehydes in methanol. The structures of the synthesized compounds were determined using data from various spectroscopic methods (IR, 1H-NMR, 13C-NMR, and LCMSMS). The compounds (50 mg/kg) were tested for their antidepressant-like effects by tail suspension and modified forced swimming tests (MFST). In addition, possible alterations in locomotor activities of mice were evaluated by activity cage measurements. Obtained results showed that compounds 2c-2f reduced the immobility time of mice in both of the antidepressant activity-screening tests indicating that these derivatives have antidepressant-like effects. Moreover, in MFST, compounds 2c and 2e significantly increased the swimming times, while compounds 2d and 2f significantly prolonged the climbing durations. Antidepressant-like effects of the compounds 2c and 2e was reversed with p-chlorophenylalanine methyl ester (serotonin depleting agent) pre-treatments while the same effect caused by the compounds 2d and 2f was abolished by pretreatment with α-methyl-para-tyrosine methyl ester (catecholamine depleting agent) pre-administrations. Moreover, pre-treatment with naloxone reversed the antidepressant-like effects of these four derivatives. Obtained results indicated that monoaminergic and opioidergic systems mediated the antidepressant-like effects of our novel piperidine derivatives.","PeriodicalId":7147,"journal":{"name":"Acta poloniae pharmaceutica","volume":" ","pages":""},"PeriodicalIF":0.4,"publicationDate":"2022-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43884592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tanja B Vojinovic, Zorica Potpara, M. Vukmirović, Nemanja Turkovic, S. Ibrić
The aim of this study was to examine the possibility of using artificial neural networks in the optimization of solid dispersions with carbamazepine. Artificial neural networks of the Generalized regression neural network type with four layers, gave models that describe the effect of components in solid dispersions carbamazepine-Neusilin ® UFL2 (magnesium aluminosilicate)-Collidon ® VA64 (vinylpyrrolidone-vinyl acetate) and dissolved carbamazepine value (%) after 10 (Q10) and 30(Q30) minutes of carbamazepine testing. After the learning process, root mean square error (RMS) values of 0.0029 were obtained for the training data set, and 0.1185 for the test training data, which is an excellent prediction of the neural network.
{"title":"Artificial neural networks and their application in the optimization of carbamazepine solid dispersions","authors":"Tanja B Vojinovic, Zorica Potpara, M. Vukmirović, Nemanja Turkovic, S. Ibrić","doi":"10.32383/appdr/154044","DOIUrl":"https://doi.org/10.32383/appdr/154044","url":null,"abstract":"The aim of this study was to examine the possibility of using artificial neural networks in the optimization of solid dispersions with carbamazepine. Artificial neural networks of the Generalized regression neural network type with four layers, gave models that describe the effect of components in solid dispersions carbamazepine-Neusilin ® UFL2 (magnesium aluminosilicate)-Collidon ® VA64 (vinylpyrrolidone-vinyl acetate) and dissolved carbamazepine value (%) after 10 (Q10) and 30(Q30) minutes of carbamazepine testing. After the learning process, root mean square error (RMS) values of 0.0029 were obtained for the training data set, and 0.1185 for the test training data, which is an excellent prediction of the neural network.","PeriodicalId":7147,"journal":{"name":"Acta poloniae pharmaceutica","volume":" ","pages":""},"PeriodicalIF":0.4,"publicationDate":"2022-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43559091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
K. Karłowicz-Bodalska, Ann M. Prochera, Adrianna Rogowska, A. Muszyńska, N. Sauer, E. Kuchar, K. Głowacka, Anna Wiela- Hojeńska
Therapeutic options are limited during pregnancy due to the safety of the foetus. Non-opioid analgesics (NOA) are among the most commonly prescribed medicaments by physicians. Many of them are available over-the-counter (OTC) without prescription and in non-pharmacy sales such as hypermarkets and petrol stations. There has been a steady increase in their sales due to their high availability, the spread of self-medication and advertising. They are used for pain of various origins, inflammatory diseases, colds and flu. Monitoring the safety of therapy with these drugs is particularly important in the population of pregnant women, due to their high popularity and the different pharmacokinetics during pregnancy. The number of clinical studies on pregnant women is very limited, so it is important to raise awareness and knowledge of the adverse effects (ADR) on the developing foetus. The aim of this study was to analyse and evaluate the safety of non-opioid analgesics in a population of pregnant women based on the results of an anonymous validated survey. It will increase the awareness and enable women to make informed decisions and consider the potential risks associated with treating or not treating pain during pregnancy and breastfeeding.
{"title":"Exposure to non-opioid analgesics during pregnancy and the risk of adverse drug reactions","authors":"K. Karłowicz-Bodalska, Ann M. Prochera, Adrianna Rogowska, A. Muszyńska, N. Sauer, E. Kuchar, K. Głowacka, Anna Wiela- Hojeńska","doi":"10.32383/appdr/154637","DOIUrl":"https://doi.org/10.32383/appdr/154637","url":null,"abstract":"Therapeutic options are limited during pregnancy due to the safety of the foetus. Non-opioid analgesics (NOA) are among the most commonly prescribed medicaments by physicians. Many of them are available over-the-counter (OTC) without prescription and in non-pharmacy sales such as hypermarkets and petrol stations. There has been a steady increase in their sales due to their high availability, the spread of self-medication and advertising. They are used for pain of various origins, inflammatory diseases, colds and flu. Monitoring the safety of therapy with these drugs is particularly important in the population of pregnant women, due to their high popularity and the different pharmacokinetics during pregnancy. The number of clinical studies on pregnant women is very limited, so it is important to raise awareness and knowledge of the adverse effects (ADR) on the developing foetus. The aim of this study was to analyse and evaluate the safety of non-opioid analgesics in a population of pregnant women based on the results of an anonymous validated survey. It will increase the awareness and enable women to make informed decisions and consider the potential risks associated with treating or not treating pain during pregnancy and breastfeeding.","PeriodicalId":7147,"journal":{"name":"Acta poloniae pharmaceutica","volume":" ","pages":""},"PeriodicalIF":0.4,"publicationDate":"2022-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45036097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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