Ibuprofen

The exact mechanism of action of ibuprofen is unknown. However, this compound is considered an NSAID and thus it is a non-selective inhibitor of cyclooxygenase, which is an enzyme involved in prostaglandin (mediators of pain and fever) and thromboxane (stimulators of blood clotting) synthesis via the arachidonic acid pathway. this compound is a non-selective COX inhibitor and hence, it inhibits the activity of both COX-1 and COX-2. The inhibition of COX-2 activity decreases the synthesis of prostaglandins involved in mediating inflammation, pain, fever, and swelling while the inhibition of COX-1 is thought to cause some of the side effects of this compound including GI ulceration.
This compound AT 25 MG/KG IV INCREASED THE PRIMARY AND TOTAL HEMOSTATIC PLUG FORMATION TIME IN RABBIT EAR CHAMBERS WITH LASER-INDUCED INJURY. THE SAME DOSE INCREASED THE NUMBER OF CUMULATIVE EMBOLI OVER A 10 MINUTE PERIOD AFTER A LASER INJURY TO ARTERIOLES. IN DOGS, DOSES OF 10, 25, AND 50 MG/KG DID NOT ENHANCE THE RELEASE OF (125)I-LABELED FIBRIN DEGRADATION PRODUCTS FROM THE THROMBI AFTER INCUBATION IN PLASMIN, BUT THE LARGEST DOSE SIGNIFICANTLY DECREASED THE THROMBUS WEIGHT 90 AND 180 MINUTES AFTER DRUG ADMINISTRATION. THUS, this compound HAD AN INHIBITORY EFFECT ON PLATELET FUNCTION IN VIVO AND IN LARGE DOSES DIMINISHED THE THROMBUS WEIGHT.
L-Arginine (L-arg) exhibits multiple biological properties and plays an important role in the regulation of different functions in pathological conditions. Many of these effects could be achieved on this amino acid serving as a substrate for the enzyme nitric oxide synthase (NOS). At the gastrointestinal level, recent reports revealed its protective activities involving a hyperemic response increasing the gastric blood flow. The aim of this study was to characterize the relationship between NOS activity/expression and prostaglandin changes (PGs) in rats gastric mucosa, with L-arg associated resistance to the nonsteroidal anti-inflammatory drug (NSAID) this compound (IBP). The protective effect of oral L-arg (100 mg/kg body wt), administerred together with IBP (100 mg/kg body wt, per os), was evident enough 90 min after drug administration, although a significant protection persisted for more than 6 hr. Pretreatment with N(G)-nitro-L-arginine (L-NNA) (40 mg/kg body wt, intraperitoneally), a competitive inhibitor of constitutive NOS, partly altered the protection afforded by the amino acid. In contrast, no changes could be observed after inducible NOS inhibition [aminoguanidine (AG) 50 mg/Kg body wt, intraperitoneally). L-arg, plus IBP, produced a significant increase of the cyclic GMP (cGMP) response in tissue samples from rat stomach, 90 min and 6 h after drug administration. iNOS activity and mRNA expression were higher in IBP-treated rats, and no differences were observed in inducible responses in the L-arg plus IBP group. No variations in the cNOS activity and expression were found among the different groups of animals assayed. The measurement of mucosal PGE2 content confirmed that biosynthesis of the eicosanoid is maintained by L-arg for over 90 min after IBP, while a total inhibition was observed 6 hr later. The mechanisms of the L-arg protective effect on the damaged induced by IBP could be explained by the different period after drug administration. The early phase is mediated by cyclooxygenase/prostaglandins pathway (COX/PGs) although NO liberated by cNOS and the guanylate cyclase/cGMP pathway could be also relevant. The later phase implicates inhibition of the iNOS/NO response.
We previously showed the non-steroidal anti-inflammatory drug (NSAID) this compound suppresses inflammation and amyloid in the APPsw (Tg2576) Tg2576 transgenic mouse. The mechanism for these effects and the impact on behavior are unknown. We now show this compound's effects were not mediated by alterations in amyloid precursor protein (APP) expression or oxidative damage (carbonyls). Six months this compound treatment in Tg+ females caused a decrease in open field behavior (p < 0.05), restoring values similar to Tg- mice. Reduced caspase activation per plaque provided further evidence for a neuroprotective action of this compound.The impact of a shorter 3 month duration this compound trial, beginning at a later age (from 14 to 17 months), was also investigated. Repeated measures ANOVA of Abeta levels (soluble and insoluble) demonstrated a significant this compound treatment effect (p < 0.05). Post-hoc analysis showed that this compound-dependent reductions of both soluble Abeta and Abeta42 were most marked in entorhinal cortex (p < 0.05). Although interleukin-1beta and insoluble Abeta were more effectively reduced with longer treatment, the magnitude of the effect on soluble Abeta was not dependent on treatment duration.
Trying to decrease the production of Amyloid beta (Abeta) has been envisaged as a promising approach to prevent neurodegeneration in Alzheimer's disease (AD). A chronic inflammatory reaction with activated microglia cells and astrocytes is a constant feature of AD. The participation of the immune system in the disease process is further documented in several retrospective clinical studies showing an inverse relationship between the prevalence of AD and nonsteroidal anti-inflammatory drug (NSAID) therapy. Previously, we demonstrated that the combination of the proinflammatory cytokines TNFalpha with IFNgamma induces the production of Abeta-42 and Abeta-40 in human neuronal cells. In the present study, the neuronal cell line Sk-n-sh was incubated for 12 h with the cyclooxygenase inhibitor this compound and subsequently stimulated with the cytokines TNFalpha and IFNgamma. This compound treatment decreased the secretion of total Abeta in the conditioned media of cytokine stimulated cells by 50% and prevented the accumulation of Abeta-42 and Abeta-40 in detergent soluble cell extracts. Viability of neuronal cells measured by detection of apoptosis was neither influenced by this compound nor by cytokine treatment. The reduction in the production of Abeta by this compound was presumably due to a decreased production of betaAPP, which in contrast to the control proteins M2 pyruvate kinase, beta-tubulin and the cytokine inducible ICAM-1 was detected at low concentration in this compound treated cells. The data demonstrate a possible mechanism how this compound may decrease the risk and delay the onset of AD.

Ibuprofen hat eine breite Palette von Anwendungen in der wissenschaftlichen Forschung:

Chemie: Als Modellverbindung in der Untersuchung von NSAR und deren Synthese.

Biologie: Untersucht wegen seiner Auswirkungen auf zelluläre Prozesse und Entzündungswege.

Medizin: Weitgehend erforscht wegen seiner therapeutischen Wirkungen bei der Behandlung von Schmerzen, Entzündungen und Fieber.

Industrie: Verwendet in der Formulierung verschiedener pharmazeutischer Produkte und als Referenzstandard in der Qualitätskontrolle.

5. Wirkmechanismus

This compound übt seine Wirkung aus, indem es das Enzym Cyclooxygenase (COX) hemmt, das an der Synthese von Prostaglandinen beteiligt ist. Prostaglandine sind Lipidverbindungen, die Entzündungen, Schmerzen und Fieber vermitteln. Durch die Hemmung von COX reduziert this compound die Produktion von Prostaglandinen und lindert so diese Symptome. This compound ist ein nicht-selektiver COX-Hemmer, der sowohl COX-1- als auch COX-2-Enzyme beeinflusst .

Ähnliche Verbindungen:

• Aspirin (Acetylsalicylsäure)
• Naproxen (2-(6-Methoxynaphthalen-2-yl)propansäure)
• Diclofenac (2-(2,6-Dichloranilino)phenylessigsäure)
• Ketoprofen (2-(3-Benzoylphenyl)propansäure)

Vergleich:

• Aspirin: Wie this compound ist Aspirin ein nicht-selektiver COX-Hemmer, hat aber ein höheres Risiko für gastrointestinale Nebenwirkungen.
• Naproxen: Ähnlich wie this compound in seiner entzündungshemmenden Wirkung, hat aber eine längere Halbwertszeit, was eine weniger häufige Dosierung ermöglicht.
• Diclofenac: Wirksamer als this compound, aber mit höheren kardiovaskulären Risiken verbunden.
• Ketoprofen: In seiner Wirkung ähnlich wie this compound, kann aber mehr gastrointestinale Beschwerden verursachen .

This compound zeichnet sich durch sein ausgewogenes Wirksamkeits- und Sicherheitsprofil aus, was es zu einem der am häufigsten verwendeten NSAR weltweit macht.

Biochemical Properties

Ibuprofen acts primarily by inhibiting the activity of cyclooxygenase (COX) enzymes, which are involved in the synthesis of prostaglandins, thromboxanes, and prostacyclin . These biomolecules play key roles in inflammation, pain, and fever. By inhibiting COX enzymes, this compound reduces the production of these compounds, thereby alleviating the associated symptoms .

Cellular Effects

This compound’s effects on cells are largely due to its inhibition of prostaglandin synthesis. Prostaglandins are involved in a variety of cellular processes, including inflammation, pain sensation, and regulation of body temperature . By reducing prostaglandin production, this compound can influence these cellular functions. For example, it can decrease inflammation by reducing the production of inflammatory prostaglandins .

Molecular Mechanism

This compound exerts its effects at the molecular level primarily through its interaction with COX enzymes. It is a non-selective inhibitor of both COX-1 and COX-2 isoforms . This compound binds to the active site of these enzymes, preventing them from converting arachidonic acid into prostaglandins .

Temporal Effects in Laboratory Settings

The effects of this compound can change over time in laboratory settings. For example, prolonged exposure to this compound can lead to the upregulation of COX-2 in certain cell types, potentially reducing the drug’s efficacy . Additionally, this compound has been shown to have a relatively short half-life in the body, which can influence its long-term effects .

Dosage Effects in Animal Models

The effects of this compound in animal models can vary depending on the dosage. At lower doses, this compound primarily acts as an analgesic and antipyretic. At higher doses, it can also exhibit anti-inflammatory effects . High doses of this compound can also lead to gastrointestinal side effects in some animals .

Metabolic Pathways

This compound is metabolized primarily in the liver, where it undergoes oxidation and conjugation reactions to form various metabolites . These metabolites are then excreted in the urine . The enzymes involved in this compound metabolism include several cytochrome P450 isoforms and uridine diphosphate glucuronosyltransferases .

Transport and Distribution

After oral administration, this compound is rapidly absorbed and widely distributed throughout the body . It can cross the blood-brain barrier and placenta, and it is also found in breast milk . This compound is bound to plasma proteins, which can influence its distribution within the body .

Subcellular Localization

As a small, lipophilic molecule, this compound can diffuse across cell membranes and distribute throughout the cell . Its primary site of action is the COX enzymes, which are located in the endoplasmic reticulum and nuclear envelope .

Synthesewege und Reaktionsbedingungen: Die Synthese von Ibuprofen erfolgt in mehreren Schritten, beginnend mit Isobutylbenzol. Ein traditionelles Verfahren beinhaltet die folgenden Schritte:

Friedel-Crafts-Acylierung: Isobutylbenzol reagiert mit Essigsäureanhydrid in Gegenwart eines Lewis-Säure-Katalysators, wie Aluminiumchlorid, zu 4-Isobutylacetophenon.

Darzens-Reaktion: Das 4-Isobutylacetophenon unterliegt einer Darzens-Reaktion mit Chloressigsäure unter Bildung eines α,β-Epoxyesters.

Hydrolyse und Decarboxylierung: Der α,β-Epoxyester wird hydrolysiert und decarboxyliert, um 4-Isobutylbenzaldehyd zu liefern.

Oxidation: Das 4-Isobutylbenzaldehyd wird zu 4-Isobutylbenzoesäure oxidiert.

Umlagerung: Die 4-Isobutylbenzoesäure unterliegt einer Hoffmann-Umlagerung unter Bildung von 2-(4-Isobutylphenyl)propansäure, die this compound ist

Industrielle Produktionsverfahren: In industriellen Umgebungen wird this compound häufig mit einem effizienteren und umweltfreundlicheren Verfahren synthetisiert, das als BHC-Verfahren (Boots-Hoechst-Celanese) bekannt ist. Dieses Verfahren reduziert die Synthese auf drei Hauptschritte:

Friedel-Crafts-Acylierung: Ähnlich dem traditionellen Verfahren.

Hydrolyse und Decarboxylierung: Der Zwischenprodukt wird in einem einzigen Schritt hydrolysiert und decarboxyliert.

Umlagerung: Der letzte Umlagerungsschritt zur Herstellung von this compound.

Arten von Reaktionen:

Veresterung: this compound kann Veresterungsreaktionen mit Alkoholen eingehen, um Ester zu bilden, die seine Löslichkeits- und Absorptionsmerkmale verbessern können.

Salzbildung: Die Carbonsäuregruppe von this compound kann mit Basen reagieren, um Salze zu bilden, wodurch seine Bioverfügbarkeit verbessert wird.

Halogenierung: This compound kann Halogenierungsreaktionen eingehen, bei denen Halogene in das Molekül eingeführt werden.

Häufige Reagenzien und Bedingungen:

Veresterung: Beinhaltet typischerweise Alkohole und Säurekatalysatoren.

Salzbildung: Beinhaltet Basen wie Natriumhydroxid oder Kaliumhydroxid.

Halogenierung: Beinhaltet Halogenierungsmittel wie Chlor oder Brom.

Hauptprodukte:

Ester: Aus Veresterungsreaktionen gebildet.

Salze: Aus Reaktionen mit Basen gebildet.

Halogenierte Derivate: Aus Halogenierungsreaktionen gebildet.

• Aspirin (acetylsalicylic acid)
• Naproxen (2-(6-methoxynaphthalen-2-yl)propanoic acid)
• Diclofenac (2-(2,6-dichloranilino)phenylacetic acid)
• Ketoprofen (2-(3-benzoylphenyl)propanoic acid)

Comparison:

• Aspirin: Like ibuprofen, aspirin is a non-selective COX inhibitor but has a higher risk of gastrointestinal side effects.
• Naproxen: Similar to this compound in its anti-inflammatory effects but has a longer half-life, allowing for less frequent dosing.
• Diclofenac: More potent than this compound but associated with higher cardiovascular risks.
• Ketoprofen: Similar in action to this compound but may cause more gastrointestinal discomfort .

This compound stands out due to its balanced efficacy and safety profile, making it one of the most commonly used NSAIDs worldwide.