Lecture 3 - Neuropharmacology Flashcards
What are the symptoms of depression?
Anhedonia
Sustained bad mood
Low serotonin –. bad mood
Low NA –> low drive
What is anhedonia?
the inability to feel pleasure in normally pleasurable activites
What are the key anti-depressants also used as anxiolytics?
Tricyclics
SSRIs
SNRIs
MAOIs
How do tric-cyclics work?
They inhibit NA and 5HT reuptake therefore increasing the synaptic concentration of both.
Give an example tri-cyclic
Amoxapine
How do SSRIs work?
They inhibit 5HT reuptake –> Increased synaptic serotonin
Give an example of an SSRI
Citalopram
How do MAOIs work?
They inhibit monoamine oxidase leading to increased synaptic NA and 5HT concentrations
Give an example MAOI
moclobemide
How do SNRIs work?
They inhibit both NA and 5HT reuptake thus increasing synaptic concentrations of NA and 5HT
Higher efficacy than try-cyclics
Give an example SNRI
Venlafaxine
How come the results of anti-depressants/anxiolytics can take weeks-months?
An increase in synaptic NA and 5HT causes increases neurogenesis int he dentate gyrus, increase in dendrite arborisation and synaptogensis and pre-synaptic desenstization
What is the key problem with developing new anti-depressants and anxiolytics?
There is a huge placebo effect
What are promising new targets for anti-depressant development?
Sodium dependent serotonin transporter and the noradrenine transporter Opoid receptors NMDA receptors mGluR5 mGluR7
Outline the process of validating a new drug target for emotional disorders
Is it localised in key areas?
Perform genetic studies: ablation, KO
Use agonists and antagonists
Drug screening for suitable antagonists
What are the patterns of communication in the nervous system?
Point to point
Diffuse modulatory
What NTs does Point to point communication use?
Glu and GABA
Outline diffuse modulatory communication
Key in anxiety and depression
NA - controls attention, drive, arusal and sleep wake
5Ht - controls mood
What disease is the cholinergic diffuse modulatory system important in?
Alzheimer’s Disease
What are the drugs currently marketed for AD and how do they work?
Exelon and Ancept target acetylcolinesterase causing an increase in ACh in the CNS compensating for degeneration
What are the problems with Exelon and Ancept, the AD drugs?
They have a low efficacy and many side effects
What disease is the dopaminergic diffuse modulatory system important in?
Parkinson’s Disease
What is important about the dorsal dopaminergic diffuse modulatory system?
It is key for movement initiation
What is important about the ventral dopaminergic diffuse modulatory system?
Involved in cognition, reward and addiction
What are the positive symptoms of schizophrenia?
Delusions Hallucinations
What are the negative symptoms of schizophrenia?
Lack of emotion
Low energy
Social isolation
When is the typical onset of schizophrenia?
Late puberty
What are the main anti-psychotics?
Chlorpromazine
Haloperidol
Atypical Anti-psychotics
Describe Chlorpromazine, the anti-psychotic
D2 receptor antagonist
Causes sleepiness, weight gain, tardive dyskinesia
Describe the anti-psychotic Haloperidol
Can cause EPS
D2 receptor antagonist
What is EPS?
Extra pyramidal symptoms including dystonia, akathasia, parkisonisn and tardive dyskinesia
Name two atypical anti-psychotics
Clozapine andOlanzapine
Describe atypical anti-psychotics
Very high affinity for the D4 receptor
EPS is reduced
Prolonged high dose causes destruction of organs
High efficacy
What is PCP?
A street drug that induces the positive symptoms of schizophrenia, enhances psychosis in patients with Schizophrenia by blocking NMDA receptors
Outline a new possible method of treating Schizophrenia
Using mGlu2/3 receptors agonists
No EPS Symptoms
Showed improvement of both positive and negative symptoms compared to Olanzapine
In rats induced epileptic seizures, not seen in humans
What is the Best reward pathway?
The Frontal Dopamine Diffuse modulatory system
How does nicotine work?
It targets alpha 7 causing increased cognition
How do amphetamines work?
They increase NA, DA and 5HT by blocking reuptake and facilitating release
How does cocaine work?
Increases DA, NA and 5HT by blocking reuptake
How does cannabis work?
It targets the CB1 receptor
How does ethanol work?
It targets the GABA a receptor causing increased function, acting as an anxiolytic and sedative
It increases DA and L glu release
What is important about mGluR7?
It is a possible target for treating alcohol dependence, as agonists reduce alcohol consumption
How does LSD 25 work?
It increases efficacy of psychoanalysis
