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PSYC476 (18)

5. Psychostimulants.docx

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Kristin Hillman

Psychostimulants8413Why take a psychostimulantsAwakeConcentrateattentivenessPerformance ADHDcognitive enhancing physicalHappiness mood changingUse these recreationallythese can segway into addictive Primary reasons for use1 To keep you awake2 To make you attentive3 To increase energy o Overall behavioural activity sustained effort4 To induce euphoria CNSFunctionality of the CNS depends on electrical excitability of neuronssynaptic transmissionHow could you decrease inhibition in the brain o GABA inhibitory neurotransmitter sedationdecrease GABAergic toneHow could you increase excitation in the brainGlutamate excitatory neurotransmitterincrease glutamergic toneIf you do this approachtake CNS and try to amp up activity what are the main problemsExcitotoxcitity SeizuresContrary to global effects of CNS depressants psychostimulantstend to work on certain pathways in the braintend to modulate synaptic activation rather than activate or depress activation level Psychostimulantsincreasing psyche activity but not globally CNS activityCatecholamine ntAll come from the same thinguse an enzyme to get DOPA then another enzyme to get Dopaminewhen you want to knock out certain parts of pathway your going to affect thousands of ntsimportnant for drug designing o if they share a common pathway and you inhibit parts of that pathway you are going to affect itDopamine DASynthesis o derived from tyrosineDOPAdopamineRelease o vesicular loading into presynaptic vesiclesReceptorsbinding o 2 subtypesD1type receptorsD1 and D5metabotropicGs o D2type receptorsD2 D3 and D4metabotropicGi gKClearance o Presynaptic transporter DATENT and OCT o Dopamine is cleared by DAT then it is broken down by monoamine oxidaseNorepinephrine NESynthesis o Derived from dopamineNEEPIReleaseVesicular loading into presynaptic vesiclesReceptorsbindingAlpha 1 1a 1b 1dmetabotropic GqAlpha 2 2a 2b 2cmetabotropic GiBeta B1 B2 B3metabotropic GsClearanceo Presynaptic transporter NETENT OCT o Cleared by NET then broken down by monoamine oxidaseCOMPTSeratonin 5HTSynthesis o Synthesized from typtophan 5hydroxytryptamineReleaseLoaded into presynaptic vesiclesReceptorsbinding5HT 3ionotropic cation influx5HT 1 and 5metabotropic Gi5HT 2metabotropic Gq5HT 4metabotropic GsClearance o Presynaptic transporter SERTtransporter that clears it o broken down by monoamine oxidaseCOMTDiagramSeratonin is either taken back up by SERT ie reuptake 3 pathway or it is bound to receptor to stop further release via 2 pathway
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