This document summarizes various preclinical models used to study antiemetic drugs and vomiting. It describes the pathogenesis of vomiting and classification of antiemetic drugs. Various animal models are discussed including dogs, cats, ferrets, monkeys, and shrews. Different emetogens used to induce vomiting, like chemotherapy drugs, apomorphine, copper sulfate, radiation, and motion are outlined. Parameters to assess vomiting like latency, number of episodes, and conditioned taste avoidance are provided. Both in vivo models in various animals and in vitro models are described. Finally, some human models of vomiting using apomorphine and ipecac are mentioned along with references.

1. ANTIEMETIC MODELS
DR PRUTHVI D
2ND YEAR PG

2. • INTRODUCTION
• PATHOGENESIS OF VOMITING
• CLASSIFICATION OF ANTI EMETIC DRUGS
• CHOICE OF ANIMALS AND EMETOGENS
• PARAMETERS OBSERVED
• INVIVO MODELS
• INVITRO MODELS
• HUMAN MODELS

3. INTRODUCTION
• NAUSEA
• EMESIS
• ACUTE EMESIS
• DELAYED EMESIS
• ANTICIPATORY EMESIS
• BREAKTHROUGH EMESIS
• PRE EJECTION
• RETCHING
• EJECTION

4. DRUGS,RADIATION,METABOLIC
PRODUCTS
MOTION
VESTIBULAR
LABYRINTH
SENSORY STIMULI
CORTEX
LIMBIC SYSTEM
SYMPATHETIC &
PARASYMPATHETIC
VISCERAL AFFERENTS
CORTICAL AFFERENTS
CEREBELLUM
VOMITING CENTRE
IN NUCLEUS
TRACTUS
SOLITARIUS
CTZ IN AREA
POSTREMA
BLOOD & CSF
VOMITING
PATHOGENESIS

6. CLASSIFICATION OF ANTIEMETICS
1. 5HT3 antagonists: ondonsetron, tropisetron, palanosetron
2. Centrally acting dopamine receptor antagonists:
prochlorperazine, chlorpromazine
3. H1 receptor antagonists ex: Cyclizine, hydroxyzine,
promethazine, diphenhydramine
4. Muscarinic antagonists ex:Scopolamine
5. Neurokinin receptor antagonists ex: Aprepitent
6. Cannabinoid receptor anatgonists ex: Dronabinol, Nabilone
7. Corticosteroids and Nsaids
8. Benzodiazepines ex: Alprazolam, Diazepam
9. Phosphorated carbohydrate solutions
1. Ex:Aqueous solutions of glucose, fructose and
phosphoric acid

7. CHOICE OF ANIMALS
• Animals normally used-not useful
• Degenerate vomiting reflex – rodents
• Commonly used animals:
• Dogs
• Cats
• Ferrets
• Monkeys
• House musk shrew(suncus murinus)
• Least shrew(cryptotis parva
• Gerbils
• Pigeons

8. SUNCUS
MURINUS

9. FERRET

10. LEAST SHREW

11. GERBIL

12. CHOICE OF EMETOGENS
• CANCER CHEMOTHERAPEUTIC AGENTS
• APOMORPHINE
• COPPER SULPHATE
• RADIATION STIMULUS
• MOTION STIMULUS

13. PARAMETERS ASSESSED
• BEHAVIOURAL CHANGES
• LATENCY TO FIRST RETCHING AND VOMITING
• NUMBER OF VOMITING EPISODES
• CONDITIONED FLAVOUR AVOIDANCE IN RATS

14. DRUG INDUCED EMESIS MODELS
CISPLATIN INDUCED EMESIS MODEL:
Causes Both Acute And Delayed Emesis
Used as emetogen to evaluate acute emesis.
Solvent normal saline at 70oC followed by slow cooling to 40oC
o DOG MODEL: described by Gylys et al. IV dose of 3.2mg/kg/ml
o CAT MODEL: described by John et al.IV dose of 3- 7.5 mg/kg
o FERRET MODEL: IV 10 mg/kg
o PIGEON MODEL: IV 4 mg/kg
o SUNCUS MURINUS MODEL: 20 mg/kg IP
o RAT MODEL: 3 to 10 mg/kg IP

15. APOMORPHINE INDUCED EMESIS MODEL
Dogs most sensitive.
Cats controversial
Suncus murinus unresponsive
o DOG MODEL: 0.3 mg/kg SC
o FERRET MODEL: 0.25 mg/kg SC
o RAT MODEL: 10 mg/kg IP
COPPER SULFATE INDUCED EMESIS MODEL
Powerful oxidizing agent
Solvent distilled water
o DOG MODEL:100 mg/kg orogastric tube
o CAT MODEL:40 mg/kg orally
o FERRET MODEL:40 mg/kg orally
o SUNCUS MURINUS MODEL:40 mg/kg orally

16. MOTION INDUCED EMESIS MODEL
o CAT MODEL: vertical osscillations @ 0.3Hz
o SUNCUS MURINUS MODEL: horizontal osscillations @ 1
Hz for 10 mnts
o RAT MODEL:
RADIATION INDUCED EMESIS MODEL
o DOG MODEL: Co 60 and 8 Gy
o FERRET MODEL: Co 60 and 201cGy
o RAT MODEL: 4 Gy
MODEL FOR ANTICIPATORY NAUSEA AND VOMITING
Emetic stimuli used are horizontal motion(1 Hz,4 cm,10
min),nicotine(4mg/kg sc),lithium chloride 100 mg/kg IP
DELAYED EMESIS MODEL- METHOTRAXATE INDUCED
MTX prepared in 5% dextrose

17. • INVITRO MODELS
• ISOLATED GUNIEA PIG COLON PREPERATION
• HUMAN MODELS
• APOMORPHINE INDUCED
• IPECAC INDUCED

18. REFERENCES
• Drug screening methods by SK Gupta
• The Pharmacological Basis of Therapeutics Goodman &
Gilman- 12th edition.
• Basic and clinical Pharmacology Betram G Katzung- 12 th
Edition
• J Clin Pharmacol. 1978 Feb-Mar;18(2-3):95-9.An
apomorphine-induced vomiting model for antiemetic studies
in man Proctor JD, Chremos AN, Evans EF, Wasserman AJ.
• Clin Pharmacol Ther. 1993 Jul;54(1):53-7.Ipecacuanha-
induced emesis: a human model for testing antiemetic drug
activity.Minton N1, Swift R, Lawlor C, Mant T, Henry J.