screening of Analgesics

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it includes the screening methods of narcotic& non-narcotic analgesics

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Screening of Analgesics:

Screening of Analgesics D.PADMINI M-Pharm(1 st year) Pharm. Chemistry Gitam University

Contents :

Contents Pain Mechanism of pain Analgesics definition Classification of analgesics Method of screening of narcotic analgesics Method of screening of non-narcotic analgesics

Pain::

Pain : Pain is the unpleasant sense or warning signal that indicates something is wrong inside or outside the body.

Mechanism of pain: Nociceptive pathway: :

Mechanism of pain: Nociceptive pathway : AA Analgesics

Analgesics :

Analgesics A drug that selectively relive pain by acting in the CNS and Peripheral pain mechanism without significantly altering consciousness.

Classification of analgesics::

Classification of analgesics: Analgesics divided into two groups: Narcotics Ex. Morphine, Pethidine Non-narcotics Ex.NSAIDS-aspirin,paracetamol

Screening of Narcotic Analgesics : :

Screening of Narcotic Analgesics : Principle :- Record the response of an animals to a painful stimulus before and after administration of analgesics.

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Categorized into: Mechanical methods: -Tail clip method -Caudal compression method Thermal methods: -Hot plate method -Tail flick method Others: -Pethidine potentiation -Nalorphine antagonism

Tail clip method::

Tail clip method: Animals : mice/rats Instruments : artery clamp, stop watch Group: 6-10 mice Test substances :12.5mg/kg morphine HCl via s.c Procedure: test sensitivity of animal to artificial pain produced by clipping artery clamp(not exceeding 15 sec)

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Administration of dose via s.c route Test sensitivity of animal to artificial pain at 30,60,90 min observed If no attempt to remove the clip is made during 15sec at one of the three observations positive analgesic response

Hot Plate Method :

Hot Plate Method Material Animal: Mouse Instrument: Hot plate analgesiometer Painful stimulus: Heat (55°C) Drug used: 0.63 mg/kg Morphine via s.c Procedure: mice dropped on hot plate ( 55°C) The reaction times taken i.e. at nearest fifth of second, 5min, 10min before drug administration(normal time)

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Drug administered s.c Reaction time taken at 10 , 20 , 30 , 45 , 60,90,120,180 and 240min The response considered positive when reaction time after drug administered is longer than 30 sec at least once Positive analgesic action

LE7406 Hot-Plate:

LE7406 Hot-Plate

Tail-flick method:

Tail-flick method Material Animal: Mouse Instrument: Tail-flick analgesiometer Painful stimulus: Heat (by applying a beam of light 130°C) Drug used: 4mg/kg Morphine hydrochloride via s.c route

Tail flick unit SOM CODE : D97/12 Model No.37360 COMPANY : UGO BASILE,ITALY.:

Tail flick unit SOM CODE : D97/12 Model No.37360 COMPANY : UGO BASILE,ITALY. March 5, 2007

Nalorphine antagonism:

Nalorphine antagonism This test is designed to show morphine like properties in a drug Animals : male rats Procedure : Toxic dose of a drug was injected to the animals Peak effects are observed 0.5- 10.0 mg/kg nalorphine inj via i.v route Reduces the toxicity

Pethidine potentiation:

Pethidine potentiation Animals : grp of 20 mice Drugs used : 2,4,8mg/kg pethidine , Test substance (25% of L D ₅₀ ) Procedure: grp of 20 mice are divided into half- groups of 10 for each of three doses of pethidine: 2,4,8mg/kg The other half given pethidine and test substance The percent analgesia is calculated with the aid of a thermal test

Screening of Non-narcotic Analgesics::

Screening of Non-narcotic Analgesics: MOA: Inhibits prostaglandin synthesis by inhibition of cycloxygenase enzyme Non-narcotic: 1- Electrical method 2- Chemical ( Writhing method)

Writhing Method:

Writhing Method Principle: The painful stimulus is induced by IP injection of an irritant substance (e.g.300mg/kg of 3% acetic acid) Writhing : Stretching of the body, withdrawing of the limb, retraction of the abdomen & the stomach touches the ground

Writhing method:

Writhing method Material Animal: Mouse Painful stimulus: Chemicals e.g.300mg/kg of 3% acetic acid Drug used: NSAID e.g. Na salicylate Procedure: grp of 6 mice taken i.p inj of 300mg/kg of 3%acetic acid given Writhing observed(control)

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Test substance given orally 15min prior to acetic acid Total no of stretching episodes observed for 20 min No of writhing observed is less compared control Positive analgesic action

Reference::

Reference: H.Gerhard Vogel’s Drug Discovery And Evaluation Pharmacological Assays 2 nd Edition,springer Verlag Berlin,germany,2002. A.Turner “Screening Methods In Pharmacology.” Www.Wikipedia.Org http://www.harvardapparatus.com/haimgs/catalog/760113_150.jpg

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