{"title":"Correction to \"Pros and cons for statins use and risk of Parkinson's disease: An updated perspective\".","authors":"","doi":"10.1002/prp2.1221","DOIUrl":"10.1002/prp2.1221","url":null,"abstract":"","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"12 3","pages":"e1221"},"PeriodicalIF":2.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11156577/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141284428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
László G Boros, Anthony M Kyriakopoulos, Carlo Brogna, Marina Piscopo, Peter A McCullough, Stephanie Seneff
{"title":"Long-lasting, biochemically modified mRNA, and its frameshifted recombinant spike proteins in human tissues and circulation after COVID-19 vaccination.","authors":"László G Boros, Anthony M Kyriakopoulos, Carlo Brogna, Marina Piscopo, Peter A McCullough, Stephanie Seneff","doi":"10.1002/prp2.1218","DOIUrl":"10.1002/prp2.1218","url":null,"abstract":"<p><p>According to the CDC, both Pfizer and Moderna COVID-19 vaccines contain nucleoside-modified messenger RNA (mRNA) encoding the viral spike glycoprotein of severe acute respiratory syndrome caused by corona virus (SARS-CoV-2), administered via intramuscular injections. Despite their worldwide use, very little is known about how nucleoside modifications in mRNA sequences affect their breakdown, transcription and protein synthesis. It was hoped that resident and circulating immune cells attracted to the injection site make copies of the spike protein while the injected mRNA degrades within a few days. It was also originally estimated that recombinant spike proteins generated by mRNA vaccines would persist in the body for a few weeks. In reality, clinical studies now report that modified SARS-CoV-2 mRNA routinely persist up to a month from injection and can be detected in cardiac and skeletal muscle at sites of inflammation and fibrosis, while the recombinant spike protein may persist a little over half a year in blood. Vaccination with 1-methylΨ (pseudouridine enriched) mRNA can elicit cellular immunity to peptide antigens produced by +1 ribosomal frameshifting in major histocompatibility complex-diverse people. The translation of 1-methylΨ mRNA using liquid chromatography tandem mass spectrometry identified nine peptides derived from the mRNA +1 frame. These products impact on off-target host T cell immunity that include increased production of new B cell antigens with far reaching clinical consequences. As an example, a highly significant increase in heart muscle 18-flourodeoxyglucose uptake was detected in vaccinated patients up to half a year (180 days). This review article focuses on medical biochemistry, proteomics and deutenomics principles that explain the persisting spike phenomenon in circulation with organ-related functional damage even in asymptomatic individuals. Proline and hydroxyproline residues emerge as prominent deuterium (heavy hydrogen) binding sites in structural proteins with robust isotopic stability that resists not only enzymatic breakdown, but virtually all (non)-enzymatic cleavage mechanisms known in chemistry.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"12 3","pages":"e1218"},"PeriodicalIF":2.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11169277/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141311393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Pharmacist intervention to improve adherence to medication among heart failure patients at North East Ethiopia hospital","authors":"Abate Wondesen Tsige, Tsegaye Ababiya Kotiso, Kassahun Dires Ayenew, Siraye Genzeb Ayele","doi":"10.1002/prp2.1199","DOIUrl":"https://doi.org/10.1002/prp2.1199","url":null,"abstract":"Heart failure (HF) is a major and growing medical problem and its management is still challenging due to the coexistence of complications, co‐morbidity, and medication non‐adherence. HF patients who are adherent to their medication have fewer HF exacerbations, improved survival, and lower healthcare expenditure. Adherence to HF medication plays a pivotal role in attaining maximal therapeutic outcomes. The aim was to assess the medication adherence of heart failure patients at Debre Berhan Comprehensive Specialized Hospital (DBCSH). A pre‐post interventional study was undertaken from July 1, 2022, to December 31, 2022, at the medical referral clinic of DBCSH. The educational interventions were provided for 6 months. Medication adherence was determined using the Morisky Green Levin Medication Adherence Scale (MGLS). The data was entered into Epidata version 4.2.0 and analyzed using SPSS version 25.0 statistical software. Descriptive statistics and binary logistic regression analysis were performed. The strength of the association between predictor variables and outcome variables was determined using a 95% confidence interval and adjusted odd ratio. In the pre‐intervention phase, 54.6% of patients had medium medication adherence, while in the post‐intervention phase, 36.4% of patients had high medication adherence and 61.9% of patients had medium medication adherence. Following the intervention, medication cost (120, 50%), inadequate availability of drugs (75, 31%), and forgetfulness (30, 13%) were the main reasons for medication non‐adherence. The presence of co‐morbidity and the number of co‐morbidity (<jats:italic>p</jats:italic> < .05) were significantly associated with the occurrence of decreased medication adherence in the pre‐intervention phase. Interventions by pharmacists to educate HF patients about the nature of their disease and providing brochures to increase awareness of their medications have been shown to improve medication adherence.","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"23 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140830174","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}
{"title":"Prediction of cell cycle distribution after drug exposure by high content imaging analysis using low‐toxic DNA staining dye","authors":"Kazuma Takeuchi, Yumiko Nishimura, Takayoshi Matsubara, Sho Isoyama, Asuka Suzuki, Masaaki Matsuura, Shingo Dan","doi":"10.1002/prp2.1203","DOIUrl":"https://doi.org/10.1002/prp2.1203","url":null,"abstract":"Interference in cell cycle progression has been noted as one of the important properties of anticancer drugs. In this study, we developed the cell cycle prediction model using high‐content imaging data of recipient cells after drug exposure and DNA‐staining with a low‐toxic DNA dye, SiR‐DNA. For this purpose, we exploited HeLa and MCF7 cells introduced with a fluorescent ubiquitination‐based cell cycle indicator (Fucci). Fucci‐expressing cancer cells were subjected to high‐content imaging analysis using OperettaCLS after 36‐h exposure to anticancer drugs; the nuclei were segmented, and the morphological and intensity properties of each nucleus characterized by SiR‐DNA staining were calculated using imaging analysis software, Harmony. For the use of training, we classified cells into each phase of the cell cycle using the Fucci system. Training data (<jats:italic>n</jats:italic> = 7500) and validation data (<jats:italic>n</jats:italic> = 2500) were randomly sampled and the binary classification prediction models for G1, early S, and S/G2/M phases of the cell cycle were developed using four supervised machine learning algorithms. We selected random forest as the model with the best performance through 10‐fold cross‐validation; the accuracy rate was approximately 75%–87%. Regarding feature importance, variables expected to be biologically related to the cell cycle, for example, signal intensity and nuclear size, were highly ranked, suggesting the validity of the model. These results showed that the cell cycle can be predicted in cancer cells by simply exploiting the current prediction model using fluorescent images of DNA‐staining dye, and the model could be applied for the use of future ex vivo drug sensitivity diagnosis.","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"72 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140830398","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}
Luis Jaramillo‐Valverde, Kelly S. Levano, David D. Tarazona, Silvia Capristano, Cesar Sanchez, Julio A. Poterico, Eduardo Tarazona‐Santos, Heinner Guio
{"title":"Pharmacogenetic variability of tuberculosis biomarkers in native and mestizo Peruvian populations","authors":"Luis Jaramillo‐Valverde, Kelly S. Levano, David D. Tarazona, Silvia Capristano, Cesar Sanchez, Julio A. Poterico, Eduardo Tarazona‐Santos, Heinner Guio","doi":"10.1002/prp2.1179","DOIUrl":"https://doi.org/10.1002/prp2.1179","url":null,"abstract":"In Peru, 29 292 people were diagnosed with tuberculosis in 2022. Although tuberculosis treatments are effective, 3.4%–13% are associated with significant adverse drug reactions, with drug‐induced liver injury (DILI) considered the most predominant. Among the first‐line antituberculosis drugs, isoniazid is the main drug responsible for the appearance of DILI. In liver, isoniazid (INH) is metabolized by N‐acetyltransferase‐2 (<jats:italic>NAT2</jats:italic>) and cytochrome P450 2E1 (<jats:italic>CYP2E1</jats:italic>). Limited information exists on genetic risk factors associated with the presence of DILI to antituberculosis drugs in Latin America, and even less is known about these factors in the native and mestizo Peruvian population. The aim of this study was to determine the prevalence of <jats:italic>NAT2</jats:italic> and <jats:italic>CYP2E1</jats:italic> genotypes in native and mestizo population. An analytical cross‐sectional analysis was performed using genetic data from mestizo population in Lima and native participants from south of Peru. <jats:italic>NAT2</jats:italic> metabolizer was determined as fast, intermediate and slow, and <jats:italic>CYP2E1</jats:italic> genotypes were classified as c1/c1, c1/c2 and c2/c2, from molecular tests and bioinformatic analyses. Of the 472 participants, 36 and 6 <jats:italic>NAT2</jats:italic> haplotypes were identified in the mestizo and native population, respectively. In mestizo population, the most frequent <jats:italic>NAT2</jats:italic>*5B and <jats:italic>NAT2</jats:italic>*7B haplotypes were associated with DILI risk; while in natives, <jats:italic>NAT2</jats:italic>*5G and <jats:italic>NAT2</jats:italic>*13A haplotypes were associated with decreased risk of DILI. For <jats:italic>CYP2E1</jats:italic>, c1/c1 and c1/c2 genotypes are the most frequent in natives and mestizos, respectively. The linkage disequilibrium of <jats:italic>NAT2</jats:italic> single nucleotide polymorphisms (SNPs) was estimated, detecting a block between all SNPs natives. In addition, a block between rs1801280 and rs1799929 for <jats:italic>NAT2</jats:italic> was detected in mestizos. Despite the limitations of a secondary study, it was possible to report associations between <jats:italic>NAT2</jats:italic> and <jats:italic>CYP2E</jats:italic> alleles with Peruvian native and mestizo by prevalence ratios. The results of this study will help the development of new therapeutic strategies for a Tuberculosis efficient control between populations.","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"292 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140798729","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}
Camilo Scherkl, Andreas D. Meid, Sven E. Cuntz, Laura Classen, Johanna Weiss, David Czock, Walter E. Haefeli
{"title":"Coadministration of fluconazole to boost subtherapeutic sirolimus concentrations: A case report","authors":"Camilo Scherkl, Andreas D. Meid, Sven E. Cuntz, Laura Classen, Johanna Weiss, David Czock, Walter E. Haefeli","doi":"10.1002/prp2.1198","DOIUrl":"https://doi.org/10.1002/prp2.1198","url":null,"abstract":"Individual sirolimus whole blood concentrations are highly variable, critically influenced by the concomitant use of cytochrome P450 (CYP) 3A inducers or inhibitors, and also modulated by food. Therapeutic drug monitoring is therefore recommended, especially at treatment start or in circumstances that can influence sirolimus exposure. In this case report, we highlight the challenge of achieving therapeutic sirolimus concentrations and present pragmatic solutions with regimen adaptions, pharmacokinetic enhancement (use of a drug–drug interaction), concentration monitoring, and subsequent modeling of population pharmacokinetics to support treatment decisions. In a 69‐year‐old female patient with allogeneic hematopoietic stem cell transplantation, tacrolimus concentrations were stable until she developed cerebral toxoplasmosis with tonic–clonic seizures. During treatment of this acute infection, tacrolimus concentrations dropped to subtherapeutic levels and remained largely unaffected by dose increases. Only the simultaneous administration of the CYP3A4 inhibitor fluconazole and a shortening of the sirolimus dosing intervals to a (non‐approved) twice‐daily administration led to successful control of the concentrations, which ultimately even made a dose reduction possible. This intervention resulted in an increase of sirolimus mean trough concentration to 5.85 ng/mL, i.e., into the desired target range. Additionally, a higher ratio of sirolimus trough levels/daily dose from 26.9 to 109 ng/mL/mg/kg/day was achieved with the initiation of fluconazole. Thus, this case report describes the use of clinical pharmacological concepts and pharmacokinetic modeling to optimize treatment strategies in an individual patient. This strategy could be generalized to other CYP inhibitors and other treatment regimens.","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"40 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140626788","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}
Kristin Sandal Berg, Ellisiv Seines, Peter Gál, Lise Løberg‐Emanuelsen, Audun Stubhaug, Erik Waage Nielsen, Olav Spigset
{"title":"Absorption and pharmacokinetics of bupivacaine after bilateral topical administration in tonsillar fossae for posttonsillectomy pain relief","authors":"Kristin Sandal Berg, Ellisiv Seines, Peter Gál, Lise Løberg‐Emanuelsen, Audun Stubhaug, Erik Waage Nielsen, Olav Spigset","doi":"10.1002/prp2.1196","DOIUrl":"https://doi.org/10.1002/prp2.1196","url":null,"abstract":"No previous studies have investigated the systemic absorption of bupivacaine when used topically for posttonsillectomy pain. The present study was undertaken to investigate the pharmacokinetics of bupivacaine after administration by a swab in the tonsillar fossae over 4 min after tonsillectomy. Eleven adult patients undergoing elective tonsillectomy were recruited. After removal of both tonsils, each of the two tonsillar fossae was covered with a swab moistened with 2 mL of bupivacaine 5 mg/mL, that is, a total of 20 mg bupivacaine. Blood samples were drawn after 0, 5, 10, 20, 30, 45, and 60 min. Bupivacaine was analyzed with an ultra‐high‐performance liquid chromatography–tandem mass spectrometry method. The highest single measured bupivacaine serum concentration was 23.2 ng/mL and took place 10 min after drug administration. Mean (±SD) C<jats:sub>max</jats:sub> was 11.4 ± 6.0 ng/mL and mean t<jats:sub>max</jats:sub> was 11.3 ± 4.7 min. Mean t<jats:sub>1/2</jats:sub> was 31.6 ± 9.3 min. As the toxic concentration threshold has been reported to be in the interval 1500–4500 ng/mL, the concentrations measured were well below 2% of the lowest cited toxic threshold. In conclusion, this study shows that applying 4 mL of bupivacaine 5 mg/mL by a swab in the tonsillar fossae posttonsillectomy yields very low plasma concentrations, suggesting its safe application without any risk of systemic toxic effects.","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"26 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140565236","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}
John P. Savaryn, Richard L. Smith, Matthew Rosebraugh, Melina Neenan, Richard Burton, Kennan Marsh, David Wagner
{"title":"Metabolite profiling of foslevodopa/foscarbidopa in plasma of healthy human participants by LC‐HRMS indicates no major differences compared to administration of levodopa/carbidopa intestinal gel","authors":"John P. Savaryn, Richard L. Smith, Matthew Rosebraugh, Melina Neenan, Richard Burton, Kennan Marsh, David Wagner","doi":"10.1002/prp2.1190","DOIUrl":"https://doi.org/10.1002/prp2.1190","url":null,"abstract":"Analysis was conducted to compare levodopa/carbidopa pharmacokinetics and drug‐related material in plasma of healthy participants after receiving a continuous infusion of Levodopa/Carbidopa Intestinal Gel (LCIG) to a continuous subcutaneous infusion of foslevodopa/foscarbidopa. Study samples were from a randomized, open‐label, 2‐period crossover study in 20 healthy participants. Participants received either 24‐h foslevodopa/foscarbidopa SC infusion to the abdomen or LCIG delivered for 24 h to the jejunum through a nasogastric tube with jejunal extension. Serial blood samples were collected for PK. Comparability of the LD PK parameters between the two treatment regimens was determined. Selected plasma samples were pooled per treatment group and per time point for metabolite profiling. LC–MS<jats:sup>n</jats:sup> was performed using high‐resolution mass spectrometry to identify drug‐related material across the dosing regimens and time points. The LD PK parameter central values and 90% confidence intervals following the foslevodopa/foscarbidopa subcutaneous infusion were between 0.8 and 1.25 relative to the LCIG infusion. With LCIG administration, LD, CD, 3‐OMD, DHPA, DOPAC, and vanillacetic acid were identified in plasma at early and late time points (0.75 and 24 h); the metabolic profile after administration of foslevodopa/foscarbidopa demonstrated the same drug‐related compounds with the exception of the administered foslevodopa. 3‐OMD and vanillacetic acid levels increased over time in both treatment regimens. Relative quantification of LC–MS peak areas showed no major differences in the metabolite profiles. These results indicate that neither the addition of monophosphate prodrug moieties nor SC administration affects the circulating metabolite profile of foslevodopa/foscarbidopa compared to LCIG.","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"14 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140565237","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}
Kyungmin Lee, Yujeong Na, Minjin Kim, Dongjin Lee, Jongseo Choi, Gwanyoung Kim, Min‐Soo Kim
{"title":"Ursodeoxycholic acid may protect from severe acute respiratory syndrome coronavirus 2 Omicron variant by reducing angiotensin‐converting enzyme 2","authors":"Kyungmin Lee, Yujeong Na, Minjin Kim, Dongjin Lee, Jongseo Choi, Gwanyoung Kim, Min‐Soo Kim","doi":"10.1002/prp2.1194","DOIUrl":"https://doi.org/10.1002/prp2.1194","url":null,"abstract":"The SARS‐CoV‐2 caused COVID‐19 pandemic has posed a global health hazard. While some vaccines have been developed, protection against viral infection is not perfect because of the urgent approval process and the emergence of mutant SARS‐CoV‐2 variants. Here, we employed UDCA as an FXR antagonist to regulate ACE2 expression, which is one of the key pathways activated by SARS‐CoV‐2 Delta variant infection. UDCA is a well‐known reagent of liver health supplements and the only clinically approved bile acid. In this paper, we investigated the protective efficacy of UDCA on Omicron variation, since it has previously been verified for protection against Delta variant. When co‐housing with an Omicron variant‐infected hamster group resulted in spontaneous airborne transmission, the UDCA pre‐supplied group was protected from weight loss relative to the non‐treated group at 4 days post‐infection by more than 5%–10%. Furthermore, UDCA‐treated groups had a 3‐fold decrease in ACE2 expression in nasal cavities, as well as reduced viral expressing genes in the respiratory tract. Here, the data show that the UDCA serves an alternative option for preventive drug, providing SARS‐CoV‐2 protection against not only Delta but also Omicron variant. Our results of this study will help to propose drug‐repositioning of UDCA from liver health supplement to preventive drug of SARS‐CoV‐2 infection.","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"118 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140565096","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}
{"title":"The role of histamine H<sub>1</sub> receptor in the anterior cingulate cortex on nociception level following acute restraint stress in male rats.","authors":"Roxana Daniali, Fatemeh Zeraati, Mozhdeh Mohammadi, Rasool Haddadi","doi":"10.1002/prp2.1188","DOIUrl":"10.1002/prp2.1188","url":null,"abstract":"<p><p>Considering the importance of pain and stress, we decided to investigate the intra-anterior cingulate cortex (ACC) microinjection of histamine and mepyramine alone and concurrently on acute pain induced by hot plate following restraint stress in male rats. 24-gauge, 10 mm stainless steel guide cannula was implanted over the ACC in the incised scalp of 4 groups. Restraint stress in healthy rats produced a significant increase (p < .05) in the pain threshold. The simultaneous microinjection of 4 μg/side histamine and 8 μg/side mepyramine as a histaminergic system inverse agonist in healthy nonrestraint animals did not affect the pain threshold. Although Histamine decreased the threshold of pain meaningfully, mepyramine elevated it in a significant manner (p < .05). In the restrained animals, intra-ACC microinjection of histamine produced no significant impact on the pain threshold. However, intra-ACC microinjection of mepyramine before histamine, significantly (p < .01) altered the result and enhanced the threshold of pain. The results of our study demonstrated that histaminergic neurons have an important role in the processing of pain in the ACC following restraint stress.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"12 2","pages":"e1188"},"PeriodicalIF":2.9,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10938791/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140120255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}