Psychopharmacology Learning Materials

Psychopharmacology    Drug     Study of drug-induce changes in: o Mood. o Sensations. o Thinking. o Behaviour. Does not mainly focus on psychedelic or recreational drugs. Majority of studies are conducted for the development, study, and use of drugs for the modification of behaviour and the alleviation of symptoms, particularly in the treatment of mental disorders. targets Receptors. Ion channels. Carriers (transporters). Enzymes. Important neurotransmitters  Acetylcholine.  Catecholamines (dopamine, noradrenaline).  Indolamines (serotonin).  Amino acids (GABA, glutamate). Psychosis  Examples include: o Schizophrenia. o Delusional disorder. o Bipolar disorder (manic-depression).  Positive (gained) symptoms: o Delusions often paranoid in nature. o Hallucinations, usually in the form of voices which are often exhortatory in their message. o Thought disorder, comprising wild trains of thought, garbled sentences and irrational conclusions, sometimes associated with the feeling that thoughts are inserted or withdrawn by an outside agency. o Abnormal behaviours, such as stereotyped movements and occasionally aggressive behaviour.  Negative (lost) symptoms: o Withdrawal from social contacts. o Flattening of emotional response. Schizophrenia  Combination of genetics and environmental factors. o Environmental: stress, use of cannabis, etc.  o Genetic: mutations in genes DISC1, Dysbindin, Neurgeulin, G72. Main theory centres on dopamine and glutamate, although other mediators, particularly serotonin, are also receiving attention. o Dopamine overactivity/glutamate underactivity supported by imaging studies. o Amphetamine use releases dopamine in the brain and can produce in humans a behavioural syndrome indistinguishable from an acute schizophrenic episode. Dopamine pathways  From the substantia nigra pars compacta and ventral tegmental area.  Mentation and mood: o Mesolimbic  cingulate cortex, hippocampus, amygdala, nucleus accumbens, medial orbitofrontal cortex. o Mesocortical  prefrontal cortex.  Extra-pyramidal: o Nigrostriatal  striatum. Antipsychotics  Mechanism of action: o Antagonist action at dopamine D2 receptors. o Antagonist action at 5-HT2A receptors (may improve prefrontal cortical function). o Numerous other effects, leading to numerous side effects.  Psychological effects: o Eliminate or reduce delusions, hallucinations, thought disorder and abnormal moods. o Reduce likelihood of future psychotic episodes (prophylactic effect).  Side effects – extrapyramidal effects: o Dystonia. o Akathisia (restlessness; both motor and cognitive). o Parkinsonism.  Typical vs. atypical. o Typical (treat positive symptoms) – e.g. thioridazine, haloperidol. o Atypical (treat both positive and negative symptoms) – e.g. quetiapine, clozapine.  Some advantages atypical antipsychotics have over typical antipsychotics: o Fewer anticholinergic side effects. o Less parkinsonian and dystonia (sustained muscle contractions cause twisting and repetitive movements or abnormal posture. o Supress the negative symptoms.  However, there are some other serious health consequences like weight gain. Summary: antipsychotics  All antipsychotic drugs are antagonists at dopamine D2-receptors (typical), but most also block other monoamine receptors, especially 5-HT2 (atypical).  Antipsychotic potency generally runs parallel to activity on D2receptors.  Therapeutic effect requires about 80% occupancy of D2-receptors by the drug.  Antipsychotics take days or weeks to work, suggesting that secondary effect (e.g. increase in GFs like BDNF or antiinflammatory effects) may be more important than simply direct D2receptor block.