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Synaptic transmission Mechanisms of drug action Drugs used with schizophrenia psychlotron.org.uk Schizophrenia: drugs Neuronal cell bodies Axons Synapses occur at the junctions psychlotron.org.uk Source: science photo library Neurones Neurones transmit signals electrically along their axons The synapses (junctions between neurones) transmit signals chemically Most drugs act by interfering with events at the synapse psychlotron.org.uk Synapses Source: neuroscience.wustl.edu Vesicles filled with neurotransmitter Synaptic cleft Location of receptors (postsynaptic density) psychlotron.org.uk Synapse psychlotron.org.uk Vesicles release neurotransmitter into synaptic cleft psychlotron.org.uk Neurotransmitter binds to receptors & activates them psychlotron.org.uk Enzymes are released to break down the neurotransmitter psychlotron.org.uk Excess neurotransmitter is taken up by the pre-synaptic neurone psychlotron.org.uk Vesicles are replenished with new & reused neurotransmitter Increase synaptic activity by: Causing more neurotransmitter to be released Introducing a chemical that acts like the neurotransmitter Preventing breakdown of neurotransmitter Preventing reuptake of neurotransmitter psychlotron.org.uk Drug Therapies Decrease activity by: Increasing rate of neurotransmitter breakdown Blocking off receptors psychlotron.org.uk Drug therapies Neuroleptics (e.g. chlorpromazine) bind to DA receptors without activating them psychlotron.org.uk Antipsychotic medication psychlotron.org.uk psychlotron.org.uk Older (typical) drugs (e.g. chlorpromazine) Short term beneficial effect in 75% of patients (Davis et al, 1989) Long term beneficial effect in 55-60% (Davis et al, 1993) Most effective against positive symptoms High risk of side effects psychlotron.org.uk Effectiveness Extrapyramidal side effects (EPS) Parkinson’s-type symptoms Postural & motor abnormalities Other side effects Sedation Weight gain Seizures psychlotron.org.uk Side effects Newer (atypical) drugs (e.g. clozapine) As effective as typical drugs on positive symptoms; better for negative symptoms (Bilder et al, 2002) More effective with treatment-resistant patients (DeNayer et al, 2003) Less risk of EPS, but other side effects may occur (e.g. blood disorders) psychlotron.org.uk Effectiveness tightly bound; slow release from receptor DA receptor Drug loosely bound; fast release from receptor psychlotron.org.uk Typical vs. atypical