BASICS OF EXPERIMENTAL PHARMACOLOGY PHARMACOLOGY is the science which deals with study of drugs EXPERIMENTAL PHARMACOLOGY: deals with effect of various pharmacological agents studied on different animal species AIMS : • Find out the therapeutic agent suitable for human use • Study the toxicity of the drugs • Study the mechanism and site of action of drugs • Pharmacology Discovery of new drugs or to study the actions of existing drugs Preclinical Clinical Two ways 1) Intact animal study – invivo 2) isolated organ study – invitro Phase -1,2,3,4 Experimental pharmacology – great imp Experimenter should take outmost care Sacrificing - humane Euthanasia – painless killing Laboratory animals – breaded and handled in laboratory •Mice •Rat •Guinea pig •Rabbits RAT species Rattus norvegicus Wister starin is commonly used Other strains – •Wistar rat •Sprague Dawley rat •Biobreeding rat Wistar rat •Long-Evans rat •Zucker rat •Hairless rats •RCS rats •Shaking rat Kawasaki Sprague Dawley rat Genetically modified rats Hairless rats Zucker rat ADVANTAGES AND CHARACTERISTICS • small in size • drug to be tested required in small quantity • vomiting center is absent – oral administration can be done • gall bladder and tonsils are absent Continuous flow of bile into intestine This facilitates the study of the drugs acting on bile, cholesterol reabsorbing ect • pancreas are diffused therefore difficult to produce panereactomy • stomach, fundus and pyloric parts are clear lining between them •Gastric acid secretion is continuous EXPERIMENTAL USE • psychopharmacological studies • study of analgesics and anticonvulsants • bioassay of various hormones, such as insulin, oxytocin, vasopressin •Study of estrus cycle, mating behavior and lactation • isolated tissue pre’s • chronic study •Gastric acid secretion • hepatotoxicity studies • study on mast cells MICE ( Mus musculus) ADVANTAGES • Smallest •Easy to handle •Cheap •Less drug required EXPERIMENTAL USES • toxicological studies • teratogenicity studies • bioassay of insulin’ screening of analgesic and anticonvulsant •Screening of chemotherapeutic agents • studies related to genetics and cancer research • drugs action on CNS Swiss albino mice are commonly used species Other strains are – Balb/C and C-57 GUINEA PIGS ( CAVIA PORCELLUS ) • docile animals • highly susceptible to TB and anaphylaxis •Highly sensitive to histamine, penicillin •Required exogenous vit c in diet EXPERIMENTAL USES • evaluation of bronchodilators • anaphylactic and immunological studies • study of histamine and antihistamines • bioassay of digitalis • evaluation of local anesthetics • hearing experiments because of sensitive cochlea • isolated tissues especially ileum, heart • study on TB and ascorbic acid metabolism RABBITS (Lupas cuniculus) • Docile animal • New Zealand white strains are widely used • it has huge caceum and long appendix • enzyme atropine esterase is present in rabbit liver and plasma so it can tolerate large doses of belladona (atropine) EXPERIMENTAL USES • pyrogen testing • bioassay of anti-diabetic, curareform drugs and sex hormones • screening of agents affecting capillary permeability • drugs used in glaucoma • pharmacokinetic studies • studies related to antifertility agents • isolated preparations like heart, duodenum, ileum, pre’s • study on local anaestetics •Study on miotic and mydratics FROGS (RANA TIGRINA) •Most commonly used in physiology, pharmacology and toxicoloty • used before 200 years • amphibian animal safe to handle •Cannot breed in lab EXPERIMENTAL USES • isolated preparations, heart, rectus abdominis muscle • drugs acting on CNS •Drugs acting on NMJ