L16 CNS Flashcards
The CNS spinal cord and brain has
- 100 Bil neurons and non-neuronal cells (glia)
- Trillions of synapses
- Synaptic plasticity
- Brain areas that form neuronal circuits
Types of drugs that act clinically on the brain
- Antidepressants
- Anxiolytic
- Analgesics
- Anaesthetics
Two types of neuronal communications
- Electrical coupling through gap junctions
- CHemical signalling through NT and synapses
NT
- Chemical messengers
- Relay info from neurons to muscles or between neurons
- Has more than one lomecular targets and their locations
4 Main neuronal communication targets
- 4) degradation of surplus transmitter
- 9) interaction iwth postsynaptic receptors
- 11) reuptake of transmitter or degradation products
- 13) interaction with presynaptic receptors
2 important receptor superfamilies
- Ligand gated ion channels (ms)
- G protein coupled receptor (s)
Both found in cell membranes
What receptor type is a GABA(A) receptor
ligand-gated ion channels
What receptor type is a µ opioid receptor
G-protein coupled receptor
What is this
- Release of transmitters (ms)
- Fast synaptic transmission
L-g ion channels
What is this
- Slow synaptic transmission
- Neuromodulation
G protein-coupled receptor
4 types of mediators
- Small-molecule mediators
- Neurotrophins
- Neuropeptides
- Lipid Mediators
Mediator
Small-molecule example, target and drug class
- GABA and serotonin
- LGIC and GCPR
- Gaba = Anxiolytics
- Serotonin= Antidepressants
Mediators
Neurotrophin: example, target and drug class
- Brain-devrived neurotrophic factor
- Kinase-linked receptors
- Antidepressants
Neuropeptides: example, target and drug class
- Endorphines
- GPCR
- Opioid analgesics
Lipid mediators: example, target and drug class
- Prostaglandins
- GPCR
Non-opioid analgesics
NT on molecular targets can be
- exciatotry
- Modulatory
- Inhibitory
Types of small NT
- GABA (1º inhibitory NT)
- Serotonin
- Glutamate (1º excitatory NT)
- Dopamine
GABA has what types of receptor superfam
LGIC and GPCR
Serotonin has what types of receptor superfam
LGIC and GPCR
Glutamate has what types of receptor superfam
LGIC and GPCR
Dopamine has what types of receptor superfam
G-protein coupled receptor
GABA(A) receptor info
- LGIC
- 19 subunits but mainly 2 alpha, 2 beta and a 3rd (to make up 5)
GABA B1 =
ligand binding
GABA(B) receptor info
- Heterodimer of B1 and B2
- B1 = ligand binding
- B2 = signalling transduction
GABA B2 =
signalling transduction
Where can GABA(A) be found
- Synapse
- Extrasynaptically (outside synapse)
Serotonin receptor (5-HT3)
- LGIC
- Excitatory
- Involved in throwing up
Serotonin (5-HTx)
x = 1, 2, 4-7
- All GPCR
- Inhibitory
- Coupled to G(ai)
Glutamate and glutamate receptors
- NMDA - glutamate and glycine are co-agonist
- Apart of LGIC
- has synaptic plasticity
Other = AMPA/ Kainate (LGIC)
5-HT(1A) receptor infor
- Somatodendric on 5HT neurons in raphe nuclei -> cause negative feedback
- Located postsynaptically in many brains regions
- Antidepressant effect (med)
- inhibitory; coupled to Gi
Cell bodies in pon, upper medulla, project to cerebellum medulla and SC
Types of dopamine receptors
- D1 (D1 and D5)
- D2 (D2, D3 and D4)
D1 types info
- High expression in nigrostriatal, mesolimbic and mesocortical areas
- Posyn D1 will ↑ locomotor activity
D2 type receptors
- Presyn: ↓ firing rate of NT release
- Postsyn: ↓ locomotor activity
- Postsyn: Inhibit prolactin secretion from pituitary gland
Dopamine 4 pathways (big)
- Substania nigra to striatum: motor control (nigrostriatal)
- Vental tegmental area to amygdala, NAc: mesolimbic path - memory, emotion and reward
- Ventral tegmental area to prefrontal cortex: mesocortical pathway - executive function and emotion
- Hypothalamus to pituitary gland: (tuberohypophyseal) endocrine control (inhib prolactin)
D
Substania nigra to striatum:
motor control (nigrostriatal)
D
Vental tegmental area to amygdala, NAc:
mesolimbic path - memory, emotion and reward
D
Ventral tegmental area to prefrontal cortex:
mesocortical pathway - executive function and emotion
D
Hypothalamus to pituitary gland:
(tuberohypophyseal) endocrine control (inhib prolactin)
Antipsychotics
- D2 antagonist
- Chronic = hyperprolactinemia
- ⤷ : ↑ prolactin secretion
- Extrapyramidal effects like akathisia
D2 antagonist
Antipsychotics
Metaclopramide
Metaclopramide
- D2 antagonist
- Antimetic effects on GI tract and CTZ
- Extrapyramidal adverse on brain
Metaclopramide PCD
- antagonist of D2
- Affinity and no efficacy
Metaclopramide PCK
- metabolised by CYP2D6
- LopP-2.6 therefor lipophilic and cross BBB
