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PubMed1997

Transgenic animals as new approaches in pharmacological studies.

Transgenic animals are becoming useful tools for pharmacological studies. The use of transgenic technology raises two types of questions, "How are transgenic animals made?" and "What types of pharmacological questions can be answered using transgenic technologies?" Answers to these questions are discussed in this review. The production of animals with specific genetic alteration can be achieved by two strategies. The first involves the simple addition of DNA sequences to the chromosomes. The second strategy is to select particular genetic loci for site-specific changes. There are two well-established procedures for simple introduction of DNA into an animal genome, pronuclear DNA injection and transduction using a retrovirus. In contrast, methods for targeting specific DNA sequences to definite sites in the chromosomes are evolving rapidly. Some of these procedures can be used in combination to make a different variety of gene alterations in animals. Pharmacological studies where transgenic technology has been extensively used are discussed, including studies in the cardiovascular system, the nervous system, the endocrine system, cancer, and toxicology.

Animals↗
PubMed2000

Sequencing the entire genomes of free-living organisms: the foundation of pharmacology in the new millennium.

The power and effectiveness of clinical pharmacology are about to be transformed with a speed that earlier in this decade could not have been foreseen even by the most astute visionaries. In the very near future, we will have at our disposal the reference DNA sequence for the entire human genome, estimated to contain approximately 3.5 billion bp. At the same time, the science of whole genome sequencing is fostering the computational science of bioinformatics needed to develop practical applications for pharmacology and toxicology. Indeed, it is likely that pharmacology, toxicology, bioinformatics, and genomics will merge into a new branch of medical science for studying and developing pharmaceuticals from molecule to bedside.

Animals↗
PubMed1995

Paediatric clinical pharmacology in the former Soviet Union: Ukraine.

Among the many challenges facing the newly created states formed in Eastern Europe and Central Asia after the collapse of the Soviet Union is the development of medical education and health care independent of many of their former ties to Moscow, Ukraine, the largest of these states following the Russian Republic, is facing many of these challenges. Paediatric clinical pharmacology is markedly underdeveloped in the Ukraine. There is little clinical pharmacology content in undergraduate medical education and essentially none in postgraduate training. Underdevelopment of paediatric clinical pharmacology also increases difficulties faced because of lack of a domestic pharmaceutical industry. This situation compounds the difficulty of how physicians in Ukraine can best learn to choose and apply rational individualized therapy.

Adolescent↗
PubMed2000

A return to the past: a student perspective on medical school pharmacology.

In 1989, the second-year medical school pharmacology course at New York Medical College was revised to help improve student and faculty morale, improve scores on class exams and the U.S. Medical Licensing Examination (USMLE), and encourage more active student participation in the course. Rather than incorporating new and innovative teaching techniques, the course adapted a more classical presentation of material. Traditional blackboard lectures replaced lectures aided by the use of slides, overheads, and extensive handouts. Transcripts and the tape recording of lectures were prohibited. Higher standards for students were set with the implementation of a passing grade, initially set at 65% and increased to 66%. Review sessions with senior graduate students were incorporated, and the use of live animal demonstrations was continued. Despite the return toward a more traditional classroom, students' satisfaction with the course continues to be high, with an overall 80% satisfaction rating. Attendance at lectures is quite high (> or = 80%). In addition, student scores on the USMLE continue to improve, and the number of students failing pharmacology continues to decrease. Overall, these trends indicate that the changes implemented in the pharmacology course at New York Medical College in 1989 successfully improved student participation in class and performance in the course and on the USMLE.

Animals↗
PubMed2003

A model of pharmacology education: the experience of Istanbul Medical Faculty.

This article describes the pharmacology education program that has been applied since 1990 at the Istanbul Medical Faculty. In Turkey, medical education lasts 6 years after 11 years of general training. Each year, approximately 350 students join the Istanbul Medical Faculty. The education is mainly in conventional form: basic sciences and elementary clinical information are given mostly as didactic lectures accompanying practical courses for small groups, with each group consisting of about 50 students during the first 3 years. In the subsequent 2 years, students have several clinical clerkships, and the last year is an internship. Pharmacology, the bridge between basic and clinical sciences, has a special place in the medical training. Accordingly, the courses were expanded to 3, 4, and 5 years, the sum of all courses being approximately 140 hours. Pharmacology education took place along with basic sciences in the first years but with clinical sciences in the later years and is based on active learning methods.

Curriculum↗
PubMed2004

Putting clinical pharmacology in context: the use of popular movies.

The usefulness of movies to illustrate the psychological and sociological conflicts of medical practice is widely recognized. However, the use of popular movies to teach less oriented medical sciences, such as pharmacology is not so common. In the present review, we report the use of three films (Awakenings, Lorenzo's Oil, and Miss Evers' Boys) as a teaching tool to allow students to better understand some conflicts which appear in the domain of clinical pharmacology. These movies may help to introduce some relevant topics such as the difficulties of planning and performing clinical research with new drugs, the need of considering bioethical principles when doing research with human beings, and the social and psychological aspects of drug therapy. The films may increase the motivation of students to understand clinical pharmacology principles and may become a driving force for an increased desire to learn.

Education, Medical, Undergraduate↗
PubMed2004

Teaching application of clinical pharmacology skills using unusual observations from clozapine overdoses.

Massive drug overdoses provide a unique opportunity to observe human pharmacokinetic data not otherwise ethically available. They can also provide practical examples for teaching thoughtful application of the principles of clinical pharmacology. Following a case of clozapine overdose in which onset of toxicity was delayed by 72 hours, a probable explanation was found in an exploration of three cases with unusual concentration-time profiles and revealed unexpected implications for the management of clozapine overdoses. The authors systematically addressed the possible mechanisms proposed in the literature for an unusual plateau in concentrations observed in three clozapine overdoses. The effects that the most commonly suggested explanations (i.e., delayed absorption and saturated or impaired metabolism) would have on both clozapine and norclozapine concentrations were then modeled using the data available from those three cases to provide an objective illustration for comparison. This exercise was then used as a teaching seminar, leading students through the steps required to reach a logical explanation for the observed delayed toxicity and to consider the implications for therapy. Delayed absorption best predicted the sustained serum clozapine and norclozapine concentrations observed in three cases, and modeling suggests that much of the drug remains in the gut, available for absorption for days following an overdose. As a seminar, the exercise provides students with a practical example of the value of systematically ruling out possible explanations by considering what effects various pharmacokinetic alterations would have on observed data. Absorption following massive clozapine overdose appears fundamentally different from that with conventional dosing. This suggests a potential for delayed or prolonged toxicity, extending well beyond the time frame predicted by its half-life, unless aggressive and sustained efforts are applied to remove clozapine from the gut. Data from drug overdoses provide opportunities to explore unusual aspects of pharmacokinetics, better understand future overdoses of the same agent, and present excellent material for teaching. A seminar illustrating the role that thoughtful application of pharmacologic principles had in addressing this case is now used to introduce the clinical aspects of pharmacology to students at our institutions.

Adult↗
PubMed1998

An assessment of two gastric transport models currently used in safety pharmacology testing.

1. The potential effects of new drugs on the digestive system can be examined in a number of model systems of which intestinal motility in the mouse and/or gastric emptying in the rat are examples recommended for safety pharmacology evaluation. 2. Intestinal motility, assessed by the transit of carmine dye in the mouse and gastric motility, assessed by stomach weight in the rat, were examined using a range of clinical drugs or potent pharmacological agents known to affect gastrointestinal function. Assessment of both models in the guinea-pig was also evaluated. 3. Activity was demonstrated with codeine, diazepam, atropine and CCK-8 (all of which inhibited gastric function). However, neither model gave consistent and reliable results with the remaining reference compounds, namely metoclopramide, bethanechol, cisapride, deoxycholate, carbachol and domperidone. 4. In conclusion, this investigation questions the usefulness of simple models of gastrointestinal transport in the rodent as a means of detecting potential effects of a new drug on the digestive system. This finding should be of concern to the pharmaceutical industry as these simple models are routinely used as part of a regulatory safety pharmacology 'package' of studies.

Animals↗
PubMed2004

Evaluating student paediatric advanced nurse practitioners' experiences of a paediatric pharmacology module: in the context of reflective learning.

An evaluation of the first paediatric pharmacology module at Master's level was undertaken. The broad aims were: to ascertain whether the participants had achieved the modular learning outcomes; how their pharmacological knowledge base had altered as a result of the module; and whether their professional practice had been influenced subsequent to undertaking the module. The findings of the 12 participants who registered on the module are reported. Three tools were utilized to generate the data for this broadly qualitative study. The findings indicated that reflective thinking at the evaluative level enabled the participants to monitor their professional and personal performance and that their critical thinking skills and confidence had increased. The questionnaire survey had some limitations, but was seen as the only feasible method of achieving a representation as to whether the module had subsequently influenced the professional practice of the participants. The data presented convincing evidence of the relevance of study of a paediatric pharmacology module at Master's level for the professional and personal development of practitioners.

Child↗
PubMed2000

[Statistical considerations for preparation of a study protocol in pharmacological studies].

In order to develop a new drug with scientific rationale, it is important to design a study properly. We suggested appropriate statistical considerations in the course of planning the study that are helpful for correct evaluation of the results of a pharmacological study, the information of which will be reflected in the planning of subsequent pharmacological and clinical studies. The statistical considerations for designing a pharmacological study are as follows: 1. clarification about the purpose of the study, 2. clear statement about the endpoint of the study, 3. framing of hypotheses, 4. selection of statistical analysis method, 5. statistical considerations about study design, 6. statistical considerations of planning about statistical analysis and describing the statistical analysis. We expect researchers will be able to obtain a more reliable conclusion by preparing a study protocol taking our suggestions into consideration.

Pharmacology↗
PubMed2006

How research in behavioral pharmacology informs behavioral science.

Behavioral pharmacology is a maturing science that has made significant contributions to the study of drug effects on behavior, especially in the domain of drug-behavior interactions. Less appreciated is that research in behavioral pharmacology can have, and has had, implications for the experimental analysis of behavior, especially its conceptualizations and theory. In this article, I outline three general strategies in behavioral pharmacology research that have been employed to increase understanding of behavioral processes. Examples are provided of the general characteristics of the strategies and of implications of previous research for behavior theory. Behavior analysis will advance as its theories are challenged.

Behavior↗
PubMed2026

Exploring the mechanism of the Lianshi Jianpi formula in treating impaired glucose tolerance: a network pharmacology, molecular docking, and experimental validation study.

OBJECTIVE: To explore the bioactive constituents, key targets, signalling pathways, and molecular mechanisms of Lianshi Jianpi formula (, LSJPF) in the treatment of impaired glucose tolerance (IGT) through network pharmacology, molecular docking, and in vivo experiments. METHODS: The active ingredients and targets of LSJPF were identified using the Traditional Chinese Medicine Systems Pharmacology and HERB databases, whereas the IGT-related targets were sourced from GeneCards, DisGeNET, and PubMed. The overlap analysis identified potential targets of LSJPF. Protein-protein interaction networks and core targets were evaluated using the Search Tool for the Retrieval of Interacting Genes/Proteins and Cytoscape, and molecular docking confirmed the binding affinities. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed using Metascape. The therapeutic mechanisms were validated in an animal IGT model. RESULTS: LSJPF contained 229 compounds, with 15 active compounds and 77 potential target proteins. The phosphatidylinositol-3-kinase (PI3K)-protein kinase B (AKT) signalling pathway emerged as a key IGT pathway. The KEGG enrichment analysis revealed the pivotal genes RAC-alpha serine/threonine-protein kinase (AKT1), heat shock protein 90 kDa alpha B1, and B-cell lymphoma 2 family protein, which predominantly interact with beta-sitosterol and beta-carotene, the major constituents of Semen Euryales, Semen lablab Album, Semen sojae Atricolor in LSJPF. Molecular docking revealed strong binding affinities between LSJPF and IGT-related targets. In an animal IGT model, LSJPF treatment prevented weight loss; reduced food and water intake; decreased blood glucose levels; improved insulin resistance; decreased serum triglyceride, cholesterol, and low-density lipoprotein cholesterol levels; alleviated liver pathology; and significantly increased the levels of phosphorylated adenosine 5'-monophosphate-activated protein kinase (AMPK), PI3K, and AKT, suggesting its potential role in regulating glucose and lipid metabolism. CONCLUSIONS: These findings reveal the potential of LSJPF as an IGT intervention that targets the AMPK/PI3K/AKT cascade, validating network pharmacology predictions and highlighting the role of multipathway mechanisms in metabolic diseases.

Molecular Docking Simulation↗
PubMed2026

Acupoint Selection Patterns and Potential Mechanisms of Acupuncture in Knee Osteoarthritis: A Combined Data Mining and Network Pharmacology Study.

OBJECTIVE: To identify the core acupoint prescription and Kellgren-Lawrence (K-L) grade-dependent compatibility patterns of acupuncture for KOA through complex network analysis, and to predict the potential molecular mechanisms underlying the core prescription via network pharmacology. METHODS: Literature was retrieved from PubMed, EMbase, Cochrane Library, Web of Science, CNKI, Wanfang, VIP, and SinoMed (inception to September 3, 2025). Frequency, association rule, complex network, and K-L grade subgroup analyses were applied. Potential targets of the core prescription were identified via network pharmacology and intersected with disease targets from OMIM, Therapeutic Target, GeneCards, and DrugBank. A protein-protein interaction (PPI) network was constructed, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to explore the potential molecular mechanisms. RESULTS: We included 522 studies, yielding 582 prescriptions involving 123 acupoints. The core prescription comprised 24 acupoints, including Dubi (ST35), Neixiyan (EX-LE4), Liangqiu (ST34), Xuehai (SP10), Zusanli (ST36), Yanglingquan (GB34), Yinlingquan (SP9), among others. K-L subgroup analysis revealed ST35, GB34, SP9, and SP10 as universal core acupoints. The mild-to-moderate subgroup mainly used local acupoints, while the moderate-to-severe subgroup centered on ST35, with increased distal acupoint usage and higher degree values. Network pharmacology analysis identified 77 overlapping targets. Core targets included tumor necrosis factor (TNF), interleukin 6 (IL6), interleukin 1 beta (IL1B), tumor protein p53 (TP53), matrix metallopeptidase 9 (MMP9), signal transducer and activator of transcription 3 (STAT3), transforming growth factor beta 1 (TGFB1), caspase 3 (CASP3), and B-cell lymphoma 2 (BCL2), which were enriched in inflammation and immunity, cartilage metabolism, and tissue repair pathways. CONCLUSION: The core acupoint prescription for KOA features local acupoints combined with distal ones, exhibiting distinct patterns across K-L grades. Our computational findings suggest that core acupoints may potentially delay knee joint degeneration by synergistically regulating inflammation, cartilage metabolism, apoptosis, and tissue repair, although these predictions require experimental validation. These findings provide preliminary evidence and a theoretical basis for standardized clinical point selection and further mechanistic research.

KOA↗
PubMed2004

Clinical pharmacology: special safety considerations in drug development and pharmacovigilance.

The dose of a drug is a major determinant of its safety, and establishing a safe dose of a novel drug is a prime objective during clinical development. The design of pre-marketing clinical trials precludes the representation of important subpopulations such as children, the elderly and people with co-morbidities. Therefore, postmarketing surveillance (PMS) activities are required to monitor the safety profile of drugs in real clinical practice. Furthermore, individual variations in pharmacogenetic profiles, the immune system, drug metabolic pathways and drug-drug interactions are also important factors in the occurrence of adverse drug reactions. Thus, the safety of a drug is a major clinical consideration before and after it is marketed. A multidisciplinary approach is required to enhance the safety profile of drugs at all stages of development, including PMS activities. Clinical pharmacology encompasses a range of disciplines and forms the backbone of drug safety consideration during clinical drug development. In this review we give an overview of the clinical drug development process and consider its limitations. We present a discussion of several aspects of clinical pharmacology and their application to enhancing drug safety. Pharmacokinetic-pharmacodynamic modelling provides a method of predicting a clinically safe dose; consideration of drug pharmacokinetics in special populations may enhance safe therapeutics in a wider spectrum of patients, while pharmacogenetics provides the possibility of genotype-specific therapeutics. Pharmacovigilance activities are also discussed. Given the complex nature and unpredictability of type B reactions, PMS activities are crucial in managing the risks drugs pose to the general population. The various aspects of clinical pharmacology discussed make a strong case for this field as the backbone of optimising and promoting safe development and use of drugs.

Adolescent↗
PubMed2005

Information extraction in the life sciences: perspectives for medicinal chemistry, pharmacology and toxicology.

Information extraction approaches have been successfully applied to mine the scientific literature in biology and medicine. So far, the main focus of research and development in this domain was on the recognition and extraction of gene and protein names in the context of molecular biology and genome research and on disease names and other medical terms in the context of clinical research. Similar to biology and medical sciences, medicinal chemistry, pharmacology and toxicology are descriptive sciences. However, information extraction approaches in these disciplines encounter a number of problems that are specific to the fact that these scientific areas are essentially centred at chemical compounds and their structures. In this review, we will give a short overview on general information extraction strategies in the life sciences and we will introduce new approaches to apply information extraction to the domain of pharmacology, medicinal chemistry and toxicology. Finally, we will emphasize on how information extraction approaches will support public and commercial research in medicinal chemistry, pharmacology and toxicology by linking information on chemical structures to biological information.

Biological Science Disciplines↗
PubMed1995

Effects of pharmacological modulation of intracellular signalling systems on retinal pigment epithelial cell attachment to extracellular matrix proteins.

Complication of retinal detachment by proliferative vitreoretinopathy (PVR) is common. In the contraction of intraocular collagen matrices which occurs in PVR cell proliferation, migration and adhesion seem to be more important than any inherent cellular contractility. The aim of this study was to investigate the pharmacological inhibition of adhesion of retinal pigment epithelial cells to extracellular matrices. The adherence of human RPE lines to a range of ten substrates was assessed to determine their preferred substrates for attachment. The effect of pharmacological inhibitors and stimulators of protein kinase C, cyclic AMP and calcium/calmodulin intracellular signal transduction systems on attachment to substrates was investigated. RPE cells showed a clear substrate preference for fibronectin, and slight preference for collagen type I. Modulation of the protein kinase C and cAMP pathways had relatively minor effects upon RPE attachment. Increasing intracellular calcium concentration reduced RPE attachment to 12% of control, whilst reducing intracellular calcium had a less marked, although significant effect. Down-regulation of calmodulin reduced attachment to 17% of control. The drug tamoxifen, and the experimental calmodulin antagonist J8, produced significant inhibition of attachment even when cells had been allowed to adhere for 24 h prior to exposure to these agents. The adhesion of RPE to extracellular matrices may be markedly affected by drugs which modulate the intracellular calcium and calmodulin signalling systems. Calmodulin antagonists warrant further investigation as possible pharmacological inhibitors of PVR.

Animals↗
PubMed2026

Network pharmacology-based prediction and experimental validation of the anti-hyperuricemic effects of oolong tea polyphenols.

OBJECTIVE: This study aimed to identify candidate therapeutic targets of oolong tea polyphenols (TP) against hyperuricemia (HUA) using network pharmacology and bioinformatics, and to validate the predicted molecular mechanism through in vivo experimentation. METHODS: Drug and disease targets were retrieved from public databases, and overlapping targets were identified by Venn diagram analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed on the shared targets, and a protein-protein interaction (PPI) network was constructed to identify hub genes. For in vivo validation, an HUA mouse model was established by 15 days of oral potassium oxonate (PO) administration. Model mice then received TP by gavage at low (0.5 g⋅kg-1⋅d-1), medium (1 g⋅kg-1⋅d-1), or high (2 g⋅kg-1⋅d-1) doses for an additional 15 days. Serum biochemical markers, histopathological changes, and pathway-related protein expression were assessed by enzyme-linked immunosorbent assay (ELISA), hematoxylin and eosin (HE) staining, and western blot analysis, respectively. RESULTS: Network pharmacology analysis identified 59 overlapping targets between TP and HUA; GO and KEGG enrichment analyses revealed that these targets were primarily associated with hormone metabolism and the PI3K-AKT signaling pathway. In the animal experiment, TP dose-dependently reduced serum uric acid (SUA) levels in hyperuricemic mice. At the molecular level, low and medium doses of TP suppressed phosphorylation of phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), and mammalian target of rapamycin (mTOR), whereas the high dose paradoxically activated this pathway and concomitantly elevated interleukin-1β levels. These findings indicate that TP modulates uric acid metabolism through a non-monotonic, dose-dependent mechanism. CONCLUSION: By combining network pharmacology with animal experiments, this study identified the PI3K/AKT/mTOR signaling pathway as a likely mediator of the anti-hyperuricemic action of oolong tea polyphenols (TP). A medium dose of TP achieved the most balanced outcome, attenuating inflammation and preserving hepatic and renal architecture; the high dose, by contrast, paradoxically elevated interleukin-1β (IL-1β) and overactivated PI3K/AKT/mTOR signaling, underscoring the importance of dose calibration. These data suggest that a medium dose of TP may represent a feasible dietary strategy against hyperuricemia. Further work-including monomer identification, direct target validation, and clinical evaluation-is warranted to confirm and extend these preclinical findings.

PI3K/Akt/mTOR signaling pathway↗
PubMed2026

Domesticated Argania spinosa in Eastern Morocco: HPLC-DAD/GC-MS Chemical Profiling, Antioxidant and Antidiabetic Activities, and Network Pharmacology-Guided Molecular Docking.

The argan tree (Argania spinosa) is an endemic Moroccan species known for its primary product, argan oil, which possesses exceptional nutritional and medicinal properties. The current study aimed to evaluate and compare the antidiabetic and antioxidant activities of argan oil obtained from the introduced and native argan tree in eastern Morocco, to analyze its chemical composition using HPLC-DAD and GC-MS, and to investigate the molecular mechanisms behind the obtained pharmacological activities through an in silico pharmacological networking and molecular docking study. The results revealed that argan oil from all three regions of Morocco (Oujda, Agadir, and Chouihya) is rich in oleic and linoleic acids as major constituents, along with the presence of significant tocopherols. Regarding the antioxidant assays, including DPPH radical scavenging and iron-reducing power tests, argan oil from Oujda exhibited the highest activity, with the lowest IC50 values of 15.25 ± 0.022 mg/mL and 28.5 ± 1.7 mg/mL, respectively. Concerning the antidiabetic activity, we found that oil from Chaouihya showed the strongest α-amylase inhibition, while Oujda oil had the highest antiglycation activity, indicating that even introduced argan trees retain potent bioactivity. The results of the in silico investigation suggested that tocopherols may contribute to the antioxidant and antidiabetic potential of argan oil, showing predicted antioxidant activity (Pa = 0.843-0.967) and favorable binding affinities toward iNOS (ΔG = -9.3 kcal mol-1) and α-glucosidase (ΔG = -8.2 kcal mol-1). The identified fatty acids also showed predicted insulin-promoting activity (Pa = 0.59-0.75) and moderate enzyme-binding potential. Pharmacological network analysis identified 51 shared genes associated with antioxidant, antidiabetic, and argan-related targets, with enrichment of the AGE-RAGE signaling pathway. These computational findings provide possible molecular associations that may help explain the observed biological activities, although they remain predictive and require experimental validation. Overall, the in silico analysis suggests that tocopherols could be among the contributors to the multi-target profile of Argania spinosa oil, while fatty acids may provide complementary effects related to glycemic regulation.

Sapotaceae↗