Neuropharmacy I Flashcards
List 3 amino acids that are NTs.
GABA- major inhibitory
Glutamate- major excitatory
Glycine- an inhibitory NT
Name 3 monoamines that are found in the brain
NA
5HT
DA
How is 5HT formed?
1) L-tryptophan to 5-hydroxy-L-tryptophan by tryptophan hydroxylase
2) 5-hydroxy-L-tryptophan to 5HT by aromatic L-amino acid decarboxylase
How is dopamine formed?
L-tyrosine to L-DOPA by tyrosine hydroxylase
L-DOPA to dopamine by DOPA decarboxylase
Which monoamines are catecholamines?
NA
DA
Which monoamine is an indolamine?
5HT
Which peptides act as NTs?
Opioids:
Enkephalins, dynorphin, endorphin
Tachykinins:
Substance P, neurokinin A &B
Is glycine stimulatory or inhibitory?
Always inhibitory
Is NA stimulatory or inhibitory?
Depends on the receptor. Can be either
Is 5HT stimulatory or inhibitory?
Depends on the receptor
Is endorphin stimulatory or inhibitory?
Inhibitory (as will all opioids)
Is substance P stimulatory or inhibitory?
Stimulatory
Give an example of an ionotropic GABA receptor
GABA(A)-R for Cl
Give an example of an metabotropic GABA receptor
GABA(B)-R (linked to G protein for K)
Give examples of an ionotropic GluR
AMPA (Na)
NMDA (Ca, Na)
Give an example of a metabotropic GluR
mGluR ( linked to G proteins)
Give an example of an ionotropic NA receptor.
There are none
Give examples of metabotropic NA receptors
Alpha 1-2
Beta 1-3
Give an example of an ionotropic serotonin receptor.
5HT(3)
Give examples of metabotropic serotonin receptors
5HT (1,2 & 4-7)
Give examples of ionotropic substance P receptors
-
Give examples of ionotropic opiate receptors
-
Give examples of ionotropic dopamine receptors
-
Give examples of metabotropic DA receptors.
D1 & D2 (GPCRs)
What type of receptors are opiate and substance P metabotropic receptors
GPCRs
Write down the 5 criteria used to define a substance as a NT?
1) must be present in the presynaptic nerve terminal
2) they must be stored in vesicles
3) they must be released upon stimulation
4) an effect must be shown with the existence of a specific receptor
5) a mechanism of effect of termination must be evident
What are the main symptoms of Parkinson’s disease
Muscle rigidity
Akinesia
Tremor at rest
What neuronal pathway is the brain degenerates to lead to Parkinson’s disease?
The nigrostriatal pathway
How is the balance of outputs from stratum to the thalamus in the direct pathway affected in Parkinson’s?
In the direct pathway, dopamine is excitatory.
A loss of dopamine gives an inhibited direct pathway
How is the balance of outputs from the stratum to the thalamus via the indirect pathway affected in Parkinson’s.
In the indirect pathway, dopamine is inhibitory. A loss of dopamine here causes the indirect pathway to be excited.
What’s happening to the basal ganglia in Parkinson’s
It’s malfunctioning, hence the rigidity
Which NT is in deficit as a result of neuronal degeneration?
DA
Which receptor does DA activate to control the direct pathway?
D1- to activate AC
What receptor does DA activate to control the indirect pathway?
D2- couples of IP(3)
What is the drug used to replenish the DA deficit in Parkinson’s?
L-DOPA
How does carbidopa enhance the concentration of L-DOPA reaching the brain?
Inhibitor of DOPA decarboxylase
Stops the conversion of L-DOPA to dopamine in the periphery
Cannot cross the BBB
How does selegiline enhance the concentration of L-DOPA reaching the brain?
MAO inhibitor
Reduced the breakdown of dopamine in the CNS
reduced neuronal degeneration to some extent
Describe a drug used to for Parkinson’s in older patients.
Bromocriptine:
Useful where L-DOPA is no longer useful
D2 agonist
Describe a drug used for Parkinson’s in younger patients.
Ropinirole:
D2 agonist
Used as a monotherapy
What are the side effects of drugs used in Parkinson’s treatment.
Dyskinesia
Psychotic effects
Reduction in prolactin release
Hypotension
Nausea
What are the type (I) symptoms of Schizophrenia?
Auditory hallucinations
Thought disorders
Delusions
Thought broadcasting
What are the negative type (II) symptoms of schizophrenia?
Lack of drive
Social withdrawal
Motor disturbance (catatonia)
How are D2 receptors targeted in schizophrenia treatment?
They are antagonised in the mesolimbic and mesocortical pathways
How are 5HT(1A) receptors targeted in treatment of schizophrenia?
Agonised for the increase of the release of dopamine form mesocortical neurones to frontal cortex
How are 5HT(2) receptors targeted in treatment of schizophrenia?
Antagonised- contribute to antipsychotic effects
Give 2 examples of typical antipsychotic drugs.
Phenothianes- chlorpromazine
Butyrophenones- haloperidol
What are the symptoms of typical antipsychotic drugs
EPS (induced Parkinson's) Dystonia Akathisia Hyperprolactinaemia Aplastic anaemia
Give an example of an atypical antipsychotic
Clozapine
Why is an atypical drug termed so
They bind weakly to the D2 receptor. Antipsychotics are made on the premise that D2 receptors need to be antagonised
Which two monoamine NTs are targeted to treat depression?
5HT and NA
How could you increase the concentration of monoamine in the synapse?
Inhibit NET
Inhibit MOA
Increases synaptic NA
Name a tricyclic antidepressant
Imipramine
How do tricyclic antidepressants work
They block the uptake of NA into the presynaptic neurone
Name a selective NA uptake blocker
Maprotiline
Name a selective serotonin reuptake blocker
Fluoxetine
How have antidepressants been improved from tricyclics
Been made to be safer in overdose by fewer side effects by making them more selective.
Name a reversible MAO inhibitor
Maclobemide
Name an irreversible MAO inhibitor
Phenelzine
What are the side effects of MAO inhibitors?
Hepatotoxicity
Insomnia
Convulsions
Postural hypotension
Irreversible MAO inhibitors can also interact with dietary tyramine which can lead to fatal hypertension
