Introduction and primary blind screening

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Introduction to biological assay, screening and primary blind screening
Ayman Barghout
Fichas por Ayman Barghout, actualizado hace más de 1 año
Ayman Barghout
Creado por Ayman Barghout hace alrededor de 8 años
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Biological screening Qualitative process in which an unknown drug's biological effect or mechanism of action is determined
Biological assays Quantitative process in which a known drug's concentration, potency or LD50 is determined
Methods of developing new drugs 1. Purification & Extraction of natural drugs. 2. Chemical synthesis of new drugs. 3. Modification of chemical structure of existing drugs.
Reasons for modification of chemical structure of existing drugs 1. Improve selectivity of drugs. 2. modify absorption - distribution or elimination. 3. Decrease the cost of the drug
Types of screening Simple and blind
Simple screening Detecting the action of a drug with expected pharmacological activity. e.g. testing the hypoglycemic effect of a derivative of sulphonylurea or metformin.
Blind screening Determining the biological effect of a newly synthesized drug
Blind screening tests Primary screening : Neuropharmacological tests. Secondary screening : in-vitro and in-vivo tests
Primary screening vs. secondary screening Not specific (predicts) vs. specific (confirms)
Neuropharmacological tests 1. Behavioural responses. 2. Neurological responses. 3. Autonomic responses
Neuropharmacological tests : Behavioural responses 1. Awareness. 2. Mood. 3. Motor activity
Behavioural responses: Awareness 1. Consciousness. 2. Visual placing (righting reflex). 3. Stereotypy. 4. Passivity.
Awareness : Consciousness Alertness → CNS stimulation Stupor → CNS depression
Awareness : Visual placing (Righting reflex) Decreased righting reflex → muscles relaxation or CNS depression
Awareness : Stereotypy In mice Circular movements → Morphine Searching movements of the head → Amphetamine
Awareness : Passivity Indication of CNS depression, muscles relaxation or paralysis
Behavioural responses : Mood 1. Grooming. 2. Vocalization. 3. Restlessness.
Mood : Grooming Increased grooming → CNS or sympathetic stimulation
Mood : Vocalization Indicates painful stimulation ( algesic or noxious stimuli)
Mood : Restlessness Indicates CNS stimulation or approach of convulsions
Behavioural responses : Motor activity 1. Spontaneous activity. 2. Reactivity. 3. Touch responses. 4. Pain responses.
Motor activity : Spontaneous activity Increased activity → CNS stimulation Decreased activity →CNS depression
Motor activity: Reactivity How reactive the animal is to changing his environment
Motor activity : Touch responses Amphetamine → increases touch response → mouse jumps upon being touched
Motor activity : Pain response Reduced pain response →CNS depression or analgesia
Neuropharmacological tests : Neurological responses 1. Reflexes. 2. CNS stimulation. 3. Muscle coordination. 4. Grip strength.
Neuropharmacological tests : Autonomic responses 1. Optical signs. 2. Secretory signs. 3. General signs.
Autonomic responses : Optical signs 1. Mydriasis vs Miosis. 2. Palpebral opening (opening of eyelids). 3. Exophthalmos (Protrusion of eyeball).
Autonomic responses : Secretory signs SLUD → Parasympathomimetic (Muscarinic activity) Note: SLUD = Salivation, Lacrimation, Urination and Diarrhea.
Autonomic responses : General signs 1. Writhing. 2. Piloerection. 3. Hypothermia. 4. Skin colour (red or white). 5. Heart rate. 6. Respiratory rate.
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