Anti-Ulcer Screening of Drugs

Methods with short descriptions

S K KANTHLAL

Amrita School of Pharmacy

Kochi

Anti Ulcer DrugsAnti Ulcer Drugs1. Pylorus Ligation (SHAY RAT)1. Pylorus Ligation (SHAY RAT)2. Stress Ulcer Model2. Stress Ulcer Model

a) Restrained induced ulcer (restrained Animal)a) Restrained induced ulcer (restrained Animal)b) cold-restraint stress (cold water immersion induced b) cold-restraint stress (cold water immersion induced

ulcer)ulcer)c) Swimming stress ulcerc) Swimming stress ulcer

3. Induced Ulcers3. Induced Ulcersa) Histamine Induced Gastric Ulcersa) Histamine Induced Gastric Ulcersb) Ethanol induced mucosal damageb) Ethanol induced mucosal damagec) Acetic acid induced Gastric ulcersc) Acetic acid induced Gastric ulcersd) d) Cysteamine Induced Duodenal UlcersCysteamine Induced Duodenal Ulcersf) Dimaprit Induced Duodenal Ulcersf) Dimaprit Induced Duodenal Ulcersg) NSAIDs g) NSAIDs (indomethacin, aspirin, and ibuprofen)(indomethacin, aspirin, and ibuprofen) induced gastric induced gastric

ulcersulcers

Model Animal Method ObservationRestrained model Albino Rats

Both sexFasting: 36 hrs

Apparatus: Specialized Galvanized steel apparatus

Tie all the limbs (in pair) in a galvanized steel window screen.(24 hrs)Test drug: 30 min before experiment

Total Acidity, Free acidity Ulcer Index (after Sacrifice)

Cold-restraint stress:

Restrained animal when subjected to cold water immersion, increases the stress & accelerates GI ulcer

Wistar ratsFasting: 16 hrs

Individually placed in restrained cagesAdminister oral test drugImmersed in water (22°C for I hr)Evan's blue (3m mg/kg) in tail vein

Stomach removed, kept in formalin over nightExamine the ulcer lesion (color) calculate the scoreLess longest--> more the protection

Stress Ulcer Model

The involvement of psycogenic factors in production of ulcers

DISECTED AND

PINNED STOMACH

Model Animal Method ObservationSwimming stress Albino Rats

Both sexFasting: 24 hrs

Test drug orallyDeep concrete tube filled with water (23°C)Allow to swin for 5 hrs

Total Acidity, Free acidity Ulcerative lesions:0- no1- dia less < 1mm2- dia 1-2mm3- dia 2-4mm4- dia >4 mm

Model Requirements Method ObservationHistamine model

(H2 Recep activation)

Male Guinea Pig (300-400gm)Histamine sulphate: 50 mg i.pFasting: 36 hrs

Test drug administeredAfter 30-45 min → ip ing of HistPromethazine Hcl 5 mg 15 min before and after HistamineLeave for 4 Hrs

Total Acidity, Free acidity Ulcer Index

Ethanol model for Mucosal damage

Absolute ethanol in fasted animal for I hr induces gastric lesion)

Wistar ratsFasting: 18 hrs

Test drug administeredAfter 30 min 1 ml oral ethanol provided

Stomach removed, total acidity, Tissues observed under light transmission densitometerLower the density → higher the damage

Chemical Induced Ulcers

Model Requirements Method ObservationAcetic acid

(Chronic model for both gastric/duodenal ulcer)

Albino rats

Cysteamine in DU

(↓ Mucous production, ↑Gastrin, gastric acid & delays GET)

Model for A- Ach, antacids, PG's, H2 antagosi

Female SD ratsCysteamine Hcl (10% in NS)

28mg/100gm – 3times at 3.5 hrs orally or 20 mg/100gm 2 times at 4 hrs sc

Sacrifice: 28 hrs after cyst

Perforating ulcers in the anterior wall of duodenum Necrosis is observed an compared

Dimaprit

Hist 2 Selective agonistSuitable for H2 blocking effect

Female SD ratsFemale GpsDimaprit: 100mg/kg

Fasting: 24 Hrs

Rats: single iv ingTest: 60 min before Dimaprit

Gps: 2 mg/kg every hr for6HrTest: 30min before 1st dose

Dissected after 1 hr. Stomach/duodenum examined for gastric erosionAcidity may be ...?