BASICS OF EXPERIMENTAL PHARMACOLOGY

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

PHARMACOLOGY is the science which deals with study of drugs

Discovery of new drugs or to study the actions of existing drugs

Preclinical Clinical

Two ways 1) Intact animal study – invivo2) isolated organ study – invitro Phase -1,2,3,4

Laboratory animals – breaded and handled in laboratory

•Mice•Rat•Guinea pig•Rabbits

RATspecies Rattus norvegicus

Wister starin is commonly used

Other strains –

Experimental pharmacology – great imp

Experimenter should take outmost care Sacrificing - humane

Euthanasia – painless killing

• Wistar rat

• Sprague Dawley rat

• Biobreeding rat

• Long-Evans rat

• Zucker rat

• Hairless rats

• RCS rats

• Shaking rat Kawasaki

Wistar rat

Hairless rats

Zucker ratSprague Dawley rat

Genetically modified rats

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 speciesOther 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