Novel Pharmacotherpies Flashcards
How were most antipsychotics developed for schizophrenia?
By design
What facts explains the power of neuronal networks?
That a standard 1 mm voxel for imaging contains 50 k neurons and 300 mil synaptic connections.
At scale that’s 100 bil neurons and several trillion connections.
How has the understanding of neurons changed since the 1900’s to now?
1900
Uncertain if they were chemical or electrical.
Ramon y Cajal
- Observed synapses
- Suggested there were transmitters that connected to receptors -Synapses effected by experience
2000
Antipsychotics target specific receptors.
What is one of the lines of evidence that dopamine excess may be an oversimplification?
That drugs that largely increase release have symptoms that are the opposite to psychosis.
How was risperidone developed and what drugs followed?
Through the examination of LSD psychosis and the attempts to block it.
Olanzapine, sertindole and quetiapine all followed. 1st line antipsychotics.
WeIght gain and cholesterol
But reduced side effects (movement)
What has been the importance of Ketamine in psychosis study, what plant is similar to and what drugs have been developed?
It encompasses the full range of symptoms.
Including negative and cognitive.
Similar effect to Ibogaine plant
Antipsychotics found to block ketamine: bitoperitii and LY-023
How does the ketamine effect the brain on a neurological level?
Usually glutamate binds to AMPA and NMDA receptors. The result is the opening of the channel to allow Na and Ca through.
This strengthens the synapse via LTP.
Ketamine blocks this process at the NMDA receptor.
What is the second site for NT on NMDA receptors and why is it important?
Glycine. GLu can be toxic so this has become the preferred route for target.
How were LY-o23 and bitopertin developed and how successful have they been?
In animal studies using ketamine model:
bitopertin blocks the glycine transporter and increases Glu.
Human trails in 300: Good for Neg
LY-023- blocks the auto receptor of glutamate so increases the availability: first trial suggests just as good without weight gain.
Why have the ketamine antipsychotics failed to gain traction?
Further studies all fail to show effectiveness.
Potentially as Ketamine type of schizo is catatonic and not paranoid.
How has the glutamate theory been resurrected?
Sodium nitroprusside was shown to also block Ketamine.
It diffuses in the body and acts as a vasodilator.
Nitris Oxide is also a NT
How does Nitris oxide work as a NT and why is it interesting?
NO is released as a result of Ca being released via the NMDA receptor. This is turn creates NO which is a gas and signals an for an increase in blood flow to the area. This is known as retrograde transmission, it was the first of its type discovered.
What has the early research shown with regards to CBD and Schizophrenia?
That is was at least as effective as Amisulpride.
And beneficial to placebo.
No side effects for CBD
How might CBD be working?
Impacts G protein on CB1 receptor and halts THC.
Endocanabinoids release 2-AG which down regulates pre-synaptic terminal via LTD using retrograde transmission.
How does Microglia work and what relationship does it have to Alzheimers and Schizophrenia?
Microglia is the phagocytic cell that recognises compliment proteins as a signal for elimination. In this way it destroys and recycles synapses.
Alzheimers is marked by as runaway reduction in synapses.
Schizophrenia in a similar way has a reduction in synapses due in mainly to the compliment protein C4A protected by minocycline.
