Psychopharmacology 1 Flashcards
(38 cards)
2 inputs and 2 outputs of neurons
Inputs:- - Chemical - Electrical Output:- - Neurotransmitter release All-or-nothing (action potential)
Permeable and impermeable substances across neuronal cell membrane
Permeable:-
- Water
- Oxygen/carbon dioxide
- Small molecules (ethanol)
- Lipophilic substances
Impermeable:-
- Charged particles (ions)
- Large polar molecules eg sugars
Channel at end of synapse
Ca2+ channel
Excitation, inhibition membrane outcomes
Membrane depolarisation
Membrane hyperpolarization
Blood- brain barrier function
Physiological barrier/interface
Separates CNS and peripheral circulation
Preserves homeostasis for optimal neuronal activity
Deficient around circumventricular organs (diffusion and allows regulation of endocrine/ANS functions)
Intraluminal capillary endothelial cells function in BBB
Tight junctions- intramembranous strands
Adhesion/maintenance/regulation
Astrocytes function in BBB
Star-shaped neuroglial
Pericytes function
Mechanical support
Phagocytosis
Induce tightness
Which factors enhance transport across BBB
Lipophiliicity, Low MW,
Facilitated diffusion
Endocytosis
Monoamines as neurotransmitters
Dopamine and serotonin
Dopamine/Noradrenaline synthesis steps
1) Tyrosine at synaptic terminal synthesised to 2) L-DOPA formed via tyrosine hydroxylase
3) Dopamine via Dopa decarboxylase
Noradrenaline formed from dopamine- beta- hydroxylase
Serotonin
Synthesized from tryptophan
1) 5- hydroxytryptophan from Tryptophan hydroxylase- rate limiting enzyme
Acetylcholine
Synthesised from choline from acetyl coenzyme A
Catalysed by choline acetyltransferase
stored in vesicles in nerve terminals
Metabolised by AChE to form choline and free acetate
Glutamate/GABA
GLUTAMTE: Main excitatory neurotransmitter of CNS
GABA: Main inhibitory neurotransmitter of brain
Synthesized from glucose in krebs cycle
GABA formed from glutamic acid decarboxylase
Glycine
Main inhibitory neurotransmitter of spinal cord/PNS
Synthesised from serine
Folate-dependent reaction
Enzymes : serine hydroxymethyltransferase
Three ways of neurotransmitter termination
1) Diffusion from synaptic cleft
2) Reuptake into presynaptic neuron (inhibition)
3) Enzymatic degradation (MAO, COMT catechol-O-methyltransferase)
AChe
TCA and MAOI drug discoveries (one of each)
Imipramide -TCA
Iproniazid- MAOI
Monoamine model
5-HT broken down by MAO into 5-HIAA
Less 5-HT and 5-HIAA in brainstem of suicide deaths
Neurogenic model
Chronic stress- hippocampal damage, cortisol levels
HPA axis overactivity , insufficient negative feedback
Elevated cortisol levels
Inflammation model
Higher inflammatory marker (Cytokine, CRP)
Decreased response to treatment
Glutamate/ GABA
Increased glutamate, decreased GABA in occipital cortex
Decreased glutamate and GABA in prefrontal cortex
Scope for glutamate antagonists- Ketamine, Blocks NMDA receptor
Ketamine separates mind and body
Antidepressants MOA
Enhance monaminergic activity in central synapses
- Inhibit reuptake
- Inhibit enzymatic degradation
- Block presynaptic autoreceptors
SSRIS/SRI/NRI
Reuptake inhibitors
TCAs, SSRIs, NRI, SNRI
NRI examples
Reboxetine