Design of competitive NMDAR Agonists

Which form of glutamate binds more strongly to NMDARs and is more active?

Which group on glutamate can cause it to become ionised and how?

Which bonds allow for rotation?

What are the two stable forms which S- glutamate is likely to resemble and what percentage of each form in solution?

What is the first stage of drug discovery?

What are the main components of glutamate?

What happens if you remove any of the component groups of glutamate?

What is added to glutamate to form NMDA (methyl-1-D-Aspartate)

What can you use to block the rotation of bonds?

What is L-CCH-I?

What is LCCG-IV

Which form of glutamate acts at mGluR?

Which form of glutamate acts at NMDAR?

What does the a-carboxylic acid group of glutamate bind to at the GluN2A receptor?
Via which bonds?

What does the terminal carboxylic acid group of glutamate bind to at the GluN2A receptor? Via which type of bond?

What does the a-amino group of glutamate bind to at the GluN2A? Via what kind of bonds?

What changes are made to to turn S-Glutamate into an NMDAR antagonist. What is this first antagonist formed called?

What is kD of R-a-aminoadipic acid?

What are the two NMDAR antagonists that can be made from R-a-aminoadipic acid? How are they made and how do they differ?

What are the Kd of R-AP5 and R-AP7? Which is therefore more potent?

How can you block NMDAR and KAR currents? What effect did adding 50uM R-AP5?

Why does the phosphonate group on AP5 mean that is is a more potent antagonist than R-a-aminoadipic acid?

What do you do to turn AP5 to CGP40116?

How do you transform AP7 into CPP? What then forms?

How do you transform CPP to CPPENE?

What are the four things that can be done to increase antagonist efficacy?

Define bioavailability

When is bioavailability studied?

What three factors can bioavailability depend on?

In what state does a drug need to be in order to cross a membrane? What type of drug is better at crossing membranes?

What can you turn a drug into to get it across the blood brain barrier - how do you this? How do you turn it back into the ionised form?

What happens to amino, carboxylic and phosphonate groups at a physiological pH?

What part of the antagonist does esterification effect?

Other than making a pro drug what adaptation can you perform on a drug to help it cross barriers?

What are the benefits of adding a biphenyl ring? (2)