anti-psychotics/neuroleptics Flashcards
Identify the 5 principal amine neurotransmitters
noradrenaline
adrenaline
dopamine
serotonin
histamine
noradrenaline pathway of the central nervous system, discuss the behaviours they regulate, and describe the mechanisms of action and protein targets of drugs which interfere with amine neurotransmission
- NAd receptors - GPCR
- locus coerillius
- behavioural arousal
- deficiency linked to depression
- a1 receptors
- motor control
- fear
- cognition
- a2 receptors
- regulation of BP, sedation, analgesia
- b1 receptors
- cortex, striatum, hippocampus
dopamine production and pathways of the central nervous system
production:
tyrosine → (tyrosine hydroxylase) ⇒ DOPA → (DOPA decarboxylase) ⇒ dopamine
pathways:
nigrostriatal pathway
- neurones in substantia nigra
- degredation of dopa neurones ⇒ parkinsons
mesocortal and mesolimbic pathways
- ventral tegmental area
- motivation, compulsion, pleasure
- drives addition (drugs)
tuberohypophyseal pathway
- cell bodies in hypothalamus, down pituitary
- controls secretion of hormones e.g prolactin
dopamine protein targets which interfere with amine neurotransmission and functions
- D1,D5
- Gs coupled receptors
- stimulation ⇒ increase AC activity ⇒ cAMP ⇒ PLC ⇒ phosphorylatio
- D2, D3, D4
- Gi coupled receptors
- inhibition ⇒ decrease AC ⇒ less cAMP ⇒ less PLC activation ⇒ less phosphorylation
- inhibit V Ca2+ channels, preventing eflux into neurones
⇒ decreased dopamine release - D2 in pituitary/ DA neurones (inhibitory autoreceptors)
- prevent DA release
- regulate prolactin release
- functions
cortex = arousal, mood
limbic system = emotion
striatum = prolactin secretion
hypothalamus/pituitary = prolactin
how do amphetamines interfere with pathways of the CNS
- taken up into neurones and into vesicles
- as it accumulates in vesicles, amine neurotransmitter builds up in cytosol of neurone
- transporters bringing amine back up into neurone, bring DA out of neurone into synapse = increased activation of receptors and release of DA
how does cocaine interfere with pathways of the CNS
inhibits transporters, doesn’t reuptake DA so more is left in synaptic cleft, activating more DA receptors = increased signalling
Describe the positive symptoms of schizophrenia
- hallucinations
- delusions
- confused/disorganised speech
- trouble concentrating
- movement disorders
Describe the negative symptoms of schizophrenia
- lack of schedule and pleasure
- speech trouble
- flattening of voice
- withdrawal
- struggling with basics of daily life
neurochemical hypotheses thought to contribute to disease pathogenesis of schizophrenia
- overactivity of mesolimbic pathway
- starts in ventral tegmental area → amygdala → cortex
- antagonist for D2 = positive symptoms
- agonist for D1 = negative symptoms
- loss of signalling in meso cortical pathways → negative symptoms
dopamine theory thought to contribute to disease pathogenesis of schizophrenia
- pathophysiology of schizophrenia is due to excessive dopaminergic neurotransmission and dysfunctional D2 signalings -> +ve symptoms
- post-synaptic dopamine receptor antagonism explains antipsychotic properties
Compare and contrast conventional and atypical antipsychotics
- Typical (1st gen) antipsychotic drugs act on the dopaminergic system, blocking the dopamine type 2 (D2) receptors.
- Atypical (2nd gen) antipsychotics have a high degree of occupancy of the serotoninergic receptors 5-HT2A
function of antipsychotics
reduce dopamine transmission
what causes positive symptoms
overactivity of mesolimbic pathway
what causes negative and cognitive symptoms
underactivity of mesocortical pathway
alternative theories explaining pathophysiology of antipsychotics
glutamate theory
- Reduced function of NMDA Glutamate receptors (eg. ketamine and phencyclidine) produce +ve, -ve and cognitive symptoms
