Pharmacological Perspectives on Mechanisms, Classification and Experimental Screening Approaches for Anti-Ulcer and Anti-Asthmatic Drugs

Abstract

Pharmacological screening is a fundamental process in drug discovery and development, involving the evaluation of drugs, herbal extracts, and chemical compounds for therapeutic potential, mechanisms of action, and safety profiles. This review focuses on in-vitro and in-vivo experimental models used for the preclinical assessment of anti-ulcer and anti-asthmatic agents. Peptic ulcer disease arises from an imbalance between aggressive factors such as gastric acid, pepsin, non-steroidal anti-inflammatory drugs (NSAIDs), and Helicobacter pylori and the protective mechanisms of the gastric mucosa. The report outlines the etiology, pathophysiology, mechanisms of action, and classification of anti-ulcer agents, alongside experimental screening models. Asthma, a chronic inflammatory airway disorder characterized by reversible bronchoconstriction and airway hyperreactivity, is also discussed with emphasis on its pharmacological screening methods, drug classifications, and mechanistic pathways. This review aims to provide a comprehensive framework for the evaluation and development of effective therapeutic agents against peptic ulcer disease and asthma.

Keywords

Introduction

Pharmacological screening is a cornerstone of modern drug discovery and development, providing a systematic approach to evaluating the biological activity of substances, including synthetic drugs, herbal extracts, and chemical compounds. The process aims to identify potential therapeutic effects, understand mechanisms of action, and assess safety or toxicity before progressing to clinical trials. By applying structured experimental protocols, pharmacological screening bridges the gap between basic laboratory research and the development of clinically viable medicines. Two primary approaches dominate pharmacological screening: In-vitro and In-vivo methods. In-vitro models, conducted in controlled laboratory environments such as test tubes, multi-well plates, or cell culture systems, include assays like enzyme inhibition, receptor binding, and cell viability tests, offering detailed insights into molecular targets and interactions. In-vivo models, performed on suitable animal species, assess the integrated effects of a compound on a living system. These models measure functional endpoints such as analgesic, anti-inflammatory, and central nervous system activities, thereby providing crucial information on pharmacokinetics, pharmacodynamics, and safety profiles^1-3.

PHARMACOLOGICAL SCREENING OF ANTI-ULCER^4-7:

Ulcer refers to a discontinuity or breaks in the lining of the stomach or duodenum due to the imbalance between aggressive factors like acid, pepsin, Helicobacter pylori, NSAIDs and protective factors like mucus, bicarbonate, prostaglandins, blood flow.

Types of Ulcers:

• Gastric Ulcer: Located in the stomach, often associated with H. pylori infection, NSAID use, or increased mucosal vulnerability.
• Duodenal Ulcer: Located in the first part of the small intestine, usually linked to excess gastric acid secretion and H. pylori infection.
• Esophageal Ulcer: Occurs in the esophagus, commonly due to acid reflux or ingestion of irritants.
• Stress Ulcer: Acute mucosal damage due to severe physical stress, burns, trauma, or surgery (e.g., Curling’s ulcer, Cushing’s ulcer).

Aetiology of Peptic Ulcers

1. Helicobacter pylori Infection: Helicobacter pylori, a Gram-negative spiral-shaped bacterium, is considered the most important etiological factor in peptic ulcer disease. It is present in more than 80% of duodenal ulcers and approximately 60% of gastric ulcers. The bacterium produces urease, leading to the formation of ammonia, which damages the gastric mucosa. Additionally, it increases gastric acid secretion and disrupts mucosal protective mechanisms, thereby contributing to ulcer formation.

2. Non-Steroidal Anti-Inflammatory Drugs (NSAIDs): NSAIDs, by inhibiting cyclooxygenase (particularly COX-1), reduce prostaglandin synthesis. This results in decreased secretion of protective mucus and bicarbonate, impairing mucosal blood flow and increasing susceptibility to mucosal injury, which predisposes to ulcer development.

3. Gastric Acid Hypersecretion: Excess gastric acid secretion is a significant factor in ulcerogenesis. Conditions such as Zollinger–Ellison syndrome, stress-related mucosal disease, and increased vagal tone can lead to hypersecretion of acid, overwhelming mucosal defences and producing ulceration.

4. Lifestyle and Dietary Factors: Lifestyle choices also contribute to ulcer formation and persistence. Smoking impairs mucosal healing, alcohol acts as a direct irritant to the gastric mucosa, and caffeine may increase gastric acid secretion. Spicy foods are not primary causative agents but can aggravate symptoms and worsen patient discomfort.

5. Psychological and Physical Stress: Stress, both psychological and physical, has been linked with peptic ulcers. Severe physical insults such as trauma, burns, or sepsis can produce stress ulcers, including Curling’s ulcer in burn patients and Cushing’s ulcer in cases of central nervous system trauma.

6. Genetic Predisposition: Genetic susceptibility also plays a role in ulcer aetiology. Individuals with blood group O show a higher prevalence of duodenal ulcers, and familial clustering has been observed, suggesting an inherited component in susceptibility to peptic ulcer disease.

Pathophysiology of Peptic Ulcers:

Ulcers result from an imbalance between damaging (aggressive) and protective (defensive) factors in the GI tract.

Aggressive Factors like HCl (Hydrochloric Acid), Pepsin – Proteolytic enzyme activated by acid, Helicobacter pylori, NSAIDs, Bile acids (especially in gastric ulcers)

Defensive Factors like Mucus layer (forms protective barrier), Bicarbonate secretion (neutralizes acid), Prostaglandins (stimulate mucus/bicarbonate, increase blood flow), Epithelial regeneration and mucosal blood flow.

Cause for Disease

Primary Causes of Ulcers:

1. Helicobacter pylori (H. pylori) Infection: H. pylori is a spiral-shaped bacterium that disrupts the protective mucus barrier of the stomach and duodenum, leading to increased vulnerability of the mucosa to gastric acid and digestive enzymes. It is recognized as the predominant cause of gastric and duodenal ulcers globally.
2. Non-Steroidal Anti-Inflammatory Drugs (NSAIDs): Drugs like aspirin, ibuprofen, and naproxen can damage the stomach lining by reducing prostaglandins that protect the mucosa.
3. Excess Acid Production (Hyperacidity): Conditions like Zollinger-Ellison syndrome cause excessive gastric acid secretion, leading to ulcers.

Other Contributing Factors:

1. Smoking: Delays ulcer healing and increases risk of recurrence.
2. Alcohol consumption: Irritates and erodes the stomach lining.
3. Stress: While not a direct cause, stress can aggravate symptoms or delay healing.

Anti-ulcer Drugs: Anti-ulcer drugs are pharmacological agents that prevent the formation of ulcers, promote healing of existing ulcers, or reduce their recurrence by decreasing gastric acid secretion, neutralizing acid, eradicating Helicobacter pylori, or enhancing gastric mucosal protection.

Classification of Anti-ulcer Drugs:

1. Reduction of gastric acid secretion:

1. H2 antihistamines: Cimetidine, Ranitidine, Famotidine, Roxatidine.
2. Proton pump inhibitors: Omeprazole, Esomeprazole, Lansoprazole, Pantoprazole, Rabeprazole, Dexrabeprazole.
3. Anticholinergic drugs: Pirenzepine, Propantheline, Oxyphenonium
4. Prostaglandin analogue: Misoprostol.

2. Neutralization of gastric acid (Antacids)

1. Systemic: Sodium bicarbonate, Sod. citrate
2. Nonsystemic: Magnesium hydroxide, Mag. trisilicate, Aluminium hydroxide gel, Magaldrate, Calcium carbonate.

3. Ulcer protectives:

Sucralfate, Colloidal Bismuth Subcitrate (CBS).

4. Anti-H. pylori drugs:

Amoxicillin, Clarithromycin, Metronidazole, Tinidazole, Tetracycline.

Mechanism of Action for Anti-ulcer drugs:

Antiulcer drugs act through various mechanisms to reduce gastric acidity, protect the gastric mucosa, and promote ulcer healing.

1. Proton pump inhibitors (such as omeprazole and pantoprazole) irreversibly inhibit the H?/K?-ATPase enzyme in gastric parietal cells, blocking the final step of acid secretion and producing profound acid suppression.
2. H?-receptor antagonists (like ranitidine and famotidine) competitively block histamine H? receptors on parietal cells, reducing cAMP-mediated stimulation of the proton pump and thereby decreasing basal and nocturnal acid secretion.
3. Antacids (e.g., magnesium hydroxide, aluminium hydroxide, calcium carbonate) neutralize existing gastric acid in the lumen, rapidly increasing pH and reducing pepsin activity for quick symptomatic relief.
4. Cytoprotective agents such as sucralfate adhere to ulcer craters forming a protective barrier while  stimulating  prostaglandin  and  bicarbonate  secretion,  whereas  misoprostol, a PGE? analogue, inhibits acid secretion and enhances mucus and bicarbonate production, especially useful in NSAID-induced ulcers. For Helicobacter pylori-associated ulcers, combination therapy with antibiotics (clarithromycin, amoxicillin, metronidazole) and a PPI eradicates the infection, preventing recurrence.
5. Anticholinergics like pirenzepine reduce vagal stimulation by blocking muscarinic receptors on parietal cells.

Anti-Ulcer Screening:

Pharmacological screening of anti-ulcer agents involves experimental evaluation of drugs or substances to determine their efficacy in preventing or healing ulcers in the gastrointestinal tract, especially in the stomach and duodenum.

Anti-Ulcer Screening Methods: In-vitro methods and In-vivo methods

In-vitro methods: Pylorus Ligation in rats, [I125 ] Gastrin Binding Assay, Tiotidine Binding Assay and H+ / K+ -ATPase Inhibition Assay

In-vivo methods: Stress Ulcer Model, Histamine Induced Gastric Ulcer, Ethanol-induced Mucosal Damage, Acetic Acid Induced Gastric Ulcer, Reserpine-Induced Chronic Ulcers and Cysteamine-Induced Duodenal Ulcer.

In-vitro methods - Pylorus Ligation in rats:

Principle:

Peptic ulcer is a gastrointestinal disease which is caused due to digestion of mucosa by excess secreted gastric acid and pepsin. It is characterized by presence of lesions in the lining (mucosa) of digestive tract. When ulcer is produced in the stomach it is called as gastric ulcer. The anti-ulcer drugs are drugs inhibit ulcer by act as following mechanism such as gastric acid secretion, neutralisation of gastric acid secretion, ulcer production and anti-Helicobacter pylori. Example of anti- ulcer drugs Ranitidine, Cimitidine, Omiprazole, Aluminium Hydroxide Gel, Sucralfate and Colloidal Bismuth Subcritrate etc. The acute gastric ulcer can be produced in laboratory animals by using the chemical substance (histamine, methylene blue, serotonin, acidic acid, indomethacine and recerpine) or surgical procedure such as pyloric ligation or acute stressful condition. The most commonly used technique is the pyloric ligation induced acid accumulation and ulcer formation. It is a simple procedure and produces that suitable number of gastric ulcers. Drugs like H2 histamine antagonist (Cimitidine) inhibit pyloric ligation induced peptic ulcer.

Requirements:

Animals: Albine Wistar Rat - 150-200 gm weight (fasted overnight).

Drugs: Ether (Anaesthetic), Cimitidine (10mg/kg, intra peritoneal route). (Stock solution containing 2mg/ml of the drug and 0.5 ml/100g of body weight of the animals).

Instruments: Dissecting microscope with 10X magnification lens. Surgical instruments like Scissors, surgical knife, suture needle, silk thread.

Procedure: Determine the weight of the animal. Calculate the required dose of cimetidine and saline for the animals. From the stock solution of cimetidine and saline provided, determine the volume of injection to be injected. Animals are divided in to two groups. Saline is to be administer to control group and cimetidine (10 mg/kg i.p) to other one group. Fasting the albino rat 24 hrs (Overnight fasting) before experiment. On the day of experiment 30 minutes prior to ligation process, the saline and cimetidine (10 mg/kg i.p) should be given. The animals anaesthetize with ether and then open the abdomen by small midline incision with 1cm length just below the sternum or xiphoid process. Then expose the stomach. Pass a thread around the pyloric sphincter and make a tight knob without causing damage to blood vessels. After ligation of stomach, place the stomach and intestine at proper position and close the abdomen wall was sealed with sutures. Clean the skin from the blood spots and apply collagen over a wound. In this method, rats are placed individually in separate cages without access to food and water during the experimental period and allowed to recover. After 4 hours of pyloric ligation, the animals are sacrificed by decapitation, and the abdomen is opened. The esophageal end of the stomach is tied, and the stomach is carefully excised. A small incision is made near the pyloric region just above the knob, and the gastric contents are collected into a graduated centrifuge tube. The volume of the gastric content is measured, and the acidity is determined by titration against 0.1 N sodium hydroxide. Subsequently, the stomach is opened along the greater curvature, gently washed under running tap water, and spread on a glass slide for examination under a 10× magnification lens. Ulcer formation is observed, the number of ulcers is recorded, and severity is scored as follows:0 – Normal colored stomach, 0.5 – Red colourations, 1– Presence of ulcer spot, 1.5 – Hemorrhage stomach, 2 – Ulcer ≥ 3 and 3 – Ulcer > 5. Mean ulcer score for each animal is expressed as ulcer index. Ulcer index is calculatedby using following formula.

Ulcer index (U_I ) = U_N + U_S + U_P X 10^-1

Where,

U_N = Average number of ulcers per animals

U_S = Average number of severity score

U_P = Percentage of animals a with ulcers.

Percentage inhibition of ulceration was calculated and compared the drug treated group animal with control group animal.

Inference: The mean ulcer score of drugs treated animal is lesser than the mean ulcer score of the control group animal. The antiulcer drug (test drug) reduces the gastric acid secretion and inhibits the ulcer formation in rat.

In-vivo method - Stress Ulcer Model:

Principle: Stress ulcers occur when the body is exposed to severe physiological or environmental stress. Factors such as increased vagal stimulation, reduced gastric mucosal blood flow, excess acid secretion, and oxidative damage contribute to mucosal injury. In laboratory models, stress can be artificially induced (e.g., by restraint, cold exposure, or water immersion), leading to reproducible gastric lesions. These models are valuable for testing anti-ulcer and cytoprotective drugs.

Common Models: Cold-Restraint Stress (CRS) Model – Animals are restrained and exposed to low temperatures and Water-Immersion Restraint Stress (WIRS) Model – Animals are restrained and partially immersed in cool water.

General Procedure (Example: Cold-Restraint Stress)

Animal Selection: Healthy Wistar rats (150–220 g) are used, fasted for 18–24 hours with free access to water.

Grouping of Animals: The experimental animals are randomly divided into three groups, each consisting of 6–8 rats. These include the control group (receiving vehicle only), the standard group (treated with a reference anti-ulcer drug), and the test group (administered the investigational drug or extract).

Dosing: Administer vehicle, standard drug (e.g., ranitidine or omeprazole), or test compound orally, 1 hour before stress.

Stress Induction: Place each rat in a ventilated restrainer and keep at 4–6 °C for 2–3 hours.

Sacrifice & Dissection: After stress exposure, animals are sacrificed humanely; the stomach is removed, opened along the greater curvature, and rinsed with saline.

Lesion Observation: Gastric mucosa is inspected for haemorrhagic spots, erosions, or ulcers.

Evaluation Parameters: Ulcer Index (UI), Gastric Juice Parameters (optional): Volume, pH, total and free acidity (titration method), Gastric Wall Mucus: Measured using Alcian blue binding assay and Histopathology: Microscopic examination for epithelial loss, haemorrhage, edema, and inflammatory cell infiltration.

Pharmacological Screening of Anti-Asthmatic Activity^8-15

Asthma is a chronic inflammatory disorder of the airways characterized by recurrent, reversible episodes of airflow obstruction in response to stimuli that are otherwise innocuous and do not affect non-asthmatic individuals. It is widely recognized as a heterogeneous condition involving multiple pathological changes, including reversible bronchoconstriction, elevated basal airway tone, infiltration and activation of eosinophils and lymphocytes, epithelial cell dysfunction and damage, smooth muscle and submucosal gland hypertrophy, submucosal fibrosis, airway wall edema, and excessive mucus production. These alterations collectively contribute to non-specific airway hyperresponsiveness to various spasmogenic stimuli, which is the hallmark of the disease. Asthma is also determined as a complex chronic inflammatory disease of the respiratory tract that involves the activation of many inflammatory and structural cells, all of which release inflammatory mediators. This condition affects over 5-10 % of the population in industrialized countries, and it is increasing in prevalence and severity.

Etiology of Asthma:

The development of asthma is multifactorial, resulting from a complex interaction between genetic predisposition and various environmental triggers.

1. Genetic Factor:  Polymorphisms in genes like ADAM33, ORMDL3, and IL4R are commonly implicated.
2. Environmental Factors:

• Allergens: Exposure to pollen, dust mites, mold, and animal dander can trigger allergic asthma.
• Respiratory Infections: Viral infections (especially RSV and rhinoviruses) in early life are known to increase asthma risk.
• Air Pollution: Urban air pollution, including ozone, nitrogen dioxide, and particulate matter, is a significant risk factor.
• Occupational Exposure: Chemicals, fumes, and dust in work environments can cause occupational asthma.

3. Lifestyle and Other Factors: Smoking and passive smoke exposure increase both the risk and severity of asthma. Obesity is increasingly recognized as a risk factor due to its role in promoting systemic inflammation. Early life antibiotic use and lack of microbial exposure (hygiene hypothesis) may skew the immune system toward an allergic phenotype.

Pathophysiology:

Asthma pathophysiology involves chronic airway inflammation, leading to airway Hyperresponsiveness, Bronchoconstriction, Mucus hypersecretion, and airway remodeling.

1. Immune Response and Inflammation: The asthmatic response typically begins when allergens are presented by antigen-presenting cells (APCs) to naive T-helper cells (Th0), which differentiate into T- helper 2 cells (Th2).

Th2 cells release cytokines such as:

• IL-4: Promotes B-cell class switching to produce IgE.
• IL-5: Recruits eosinophils, which contribute to tissue damage.
• IL-13: Enhances goblet cell metaplasia and mucus production.

2. Mast Cell Activation and Bronchoconstriction: Allergen cross-linking with IgE on mast cells leads to the release of histamine, leukotrienes (LTs), and prostaglandins, causing:    Smooth muscle contraction (bronchoconstriction), Increased vascular permeability, Mucosal edema and mucus secretion.
3. Airway Hyperresponsiveness (AHR): AHR is the exaggerated airway narrowing in response to various stimuli (cold air, exercise, irritants). Mediated by eosinophils, mast cells, and cytokines, leading to smooth muscle hypertrophy and neural reflex enhancement.
4. Airway Remodelling: Chronic inflammation leads to structural changes in the airways: Subepithelial fibrosis, Smooth muscle hypertrophy, Angiogenesis, Goblet cell hyperplasia. These changes may cause irreversible airflow limitation in some patients.

Causes: Being in an urban region, especially the inner city, which may increase vulnerability to environmental pollutants Smoking or exposure to secondhand smoke, Exposure to occupational pollutants, such as chemicals used in farming and hairdressing, and in paint, steel, plastics and electronics manufacturing, Having one or both parents with asthma, Respiratory infections in childhood Low birth weight, Obesity, Gastro esophageal reflux disease (GERD).

Classification of Anti-Asthmatic Drug:

1. Bronchodilators
   1. Sympathomimetics (β2-agonists)

• Short-acting: Salbutamol, Terbutaline
• Long-acting: Salmeterola, Formoterol
• Ultra-long-acting: Indacaterol
  2. Anticholinergics (Muscarinic antagonists)

• Short-acting: Ipratropium
• Long-acting: Tiotropium
  3. Methylxanthines
     • Theophylline, Aminophylline

2. Anti-inflammatory Agents
   1. Corticosteroids

• Inhaled: Beclomethasone, Budesonide, Fluticasone
• Oral/IV: Prednisolone, Hydrocortisone
  2. Mast Cell Stabilizers
     • Cromolyn sodium, Nedocromil
  3. Leukotriene Modifiers

• Receptor antagonists: Montelukast, Zafirlukast
• 5-LOX inhibitor: Zileuton
  4. Monoclonal Antibody

• Omalizumab (Anti-IgE)

3. Miscellaneous

• Mucolytics: N-acetylcysteine
• Expectorants: Guaifenesin
• Magnesium sulfate (used IV in acute severe asthma)

Mechanism of Action of Anti-Asthmatic Drugs

1. β2-Adrenergic Agonists

β2-adrenergic agonists act by stimulating β2-adrenergic receptors located on bronchial smooth muscle. This activation stimulates adenylyl cyclase, leading to an increase in intracellular cyclic AMP (cAMP). Elevated cAMP activates protein kinase A (PKA), which phosphorylates and inactivates myosin light-chain kinase (MLCK), resulting in relaxation of bronchial smooth muscle and subsequent bronchodilation. In addition, these agents inhibit mast cell degranulation, thereby reducing the release of inflammatory mediators.

2. Anticholinergic Drugs

Anticholinergics produce bronchodilation by competitively blocking muscarinic M3 receptors on airway smooth muscle. By preventing acetylcholine (ACh) from binding, they inhibit vagally mediated bronchoconstriction and reduce vagal tone in the airways. Importantly, they caus) enzymes, particularly PDE4, which prevents the breakdown of cAMP and thereby sustains bronchodilation. They also block adenosine receptors (A1 and A2), which reduces bronchoconstriction and mast cell mediator release. Additionally, methylxanthines possess anti-inflammatory properties by inhibiting cytokine release and reducing airway inflammation.

3. Corticosteroids

Corticosteroids act through binding to glucocorticoid receptors and translocating into the nucleus, where they alter gene transcription. They suppress phospholipase A2 activity by upregulating lipocortin-1 (annexin-1), which decreases the production of arachidonic acid, e bronchodilation without impairing mucociliary clearance.

4. Methylxanthines

Methylxanthines, such as theophylline, exert their bronchodilator effect primarily by inhibiting phosphodiesterase (PDE prostaglandins, and leukotrienes. Corticosteroids also inhibit cytokine production, reduce eosinophil infiltration, and lower mast cell numbers. Furthermore, they enhance β2-receptor expression, thereby potentiating the effects of β2-agonists. Their primary role is anti-inflammatory rather than direct bronchodilation.

5. Mast Cell Stabilizers

Mast cell stabilizers function by stabilizing mast cell membranes and preventing degranulation. As a result, the release of histamine, leukotrienes, prostaglandins, and other inflammatory mediators is inhibited. They also act on sensory nerve endings, thereby reducing cough and bronchial hyperresponsiveness. These agents are mainly used for prophylaxis rather than acute treatment.

6. Leukotriene Modifiers
   1. Leukotriene Receptor Antagonists: These drugs block the effects of leukotrienes (LTC4, LTD4, LTE4) by competitively antagonizing CysLT1 receptors on bronchial smooth muscle and eosinophils. This leads to a reduction in bronchoconstriction, mucus secretion, vascular permeability, and eosinophil recruitment.
   2. 5-Lipoxygenase Inhibitors: By inhibiting the 5-lipoxygenase enzyme, these agents block the synthesis of leukotrienes from arachidonic acid, thereby reducing bronchospasm and airway inflammation.

7. Anti-IgE Monoclonal Antibodies

Anti-IgE therapy involves recombinant humanized monoclonal antibodies that bind to free IgE, preventing it from attaching to FcεRI receptors on mast cells and basophils.         This inhibition blocks the IgE-mediated allergen response, thereby decreasing the release of histamine and other inflammatory mediators. These drugs are mainly used in moderate to severe allergic asthma that is not adequately controlled by inhaled corticosteroids.

Anti-asthma Screening Methods: In-vitro methods and In-vivo methods

In-vitro method: Histamine receptor assay, Cultex technique, WST assay, Spasmolytic activity in guinea pig lungs and Vascular and airway responses to isolated lung.

In-vivo method: Bronchospasmolytic activity in anaesthetized guinea pigs, Arachidonic acid induced respiratory vascular dysfunction, Anaphylactic microshock, Serotonin aerosol induced asphyxia, Histamine induced bronchoconstriction, Pnematography in guinea pigs, Bronchial hyperactivity in guinea pigs.

In-vitro method:

Cultex Techniques:

Principle: The Cultex technique is an in-vitro method used to study the effect of airborne pollutants on respiratory cells, particularly for assessing asthmatic activity. It involves cultivating cells like human bronchial epithelial cells, on a porous membrane at the air-liquid interface, allowing for direct exposure to gaseous or particulate substances. This technique is particularly useful for studying the effects of complex mixtures, such as cigarette smoke, on cellular responses relevant to asthma.

Procedures and methodology: Bronchial epithelial cells washed with Phosphate Buffered Saline. Incubate with test drug for 24 hrs. Then cells exposed to clean air /different concentrations of smoke for 1 hour (cell exposure unit). After exposure the cells are analyzed various endpoints such as cell viability inflammatory markers, or other indicators of asthmatic activity.

In-vivo method:

Histamine induced bronchoconstriction:

Animal used -Guinea pig (400-600gm)

Anaesthetic used-Pentobarbitone 70mg/kg i.p.

Principle: Histamine induced bronchoconstriction in asthma involves the narrowing of airways due to the contraction of airway smooth muscle, primarily triggered by histamine. This process is particularly significant in asthmatics due to their heightened airway hyperresponsiveness. Histamine, a potent bronchoconstriction, can act directly by binding to H1 receptor on airway smooth muscle or indirectly by stimulating vagal nerve fibers.

Procedure: Histamine intravenous injection (decreased LC and increase PR by 200%). Repeat after 5 minutes. After Three reproducible responses. Test drug given intravenously one minute before histamine injection. Inhibition of histamine induced bronchoconstriction recorded.

CONCLUSION:

Pharmacological screening serves as a vital foundation for the discovery and development of novel therapeutic agents against peptic ulcer disease and asthma. Both conditions are characterized by complex pathophysiological mechanisms, involving an imbalance between aggressive and protective factors in ulcers and chronic airway inflammation in asthma. The use of systematic in-vitro and in-vivo models allows researchers to evaluate drug efficacy, mechanism of action, and safety profiles before clinical application. Anti-ulcer agents, through mechanisms such as suppression of gastric acid secretion, enhancement of mucosal protection, and eradication of Helicobacter pylori, play a critical role in ulcer management. Similarly, anti-asthmatic drugs, including bronchodilators, corticosteroids, mast cell stabilizers, leukotriene modifiers, and monoclonal antibodies, target different pathways of bronchoconstriction and airway inflammation to improve disease outcomes. The comprehensive understanding of pharmacological screening not only accelerates drug discovery but also ensures the rational development of safer and more effective therapies for these prevalent disorders.

ACKNOWLEDGEMENT

The authors gratefully acknowledge the Department of Pharmacology and the management of JKK Munirajah Institute of Health Sciences College of Pharmacy for their guidance, support, and provision of library facilities that enabled the successful completion of this review.

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