Midafotel

Midafotel (CPPene; SDZ EAA 494) is a potent, competitive antagonist at the NMDA receptor.^[1] It was originally designed as a potential therapy for excitotoxicity,^[2] epilepsy or neuropathic pain.^[3] It looked very promising in in vitro trials proving to be a potent competitive antagonist at the NMDA without affecting other receptors.^[4] Research continued through to in vivo cat studies where it proved to limit damage after occluding the middle cerebral artery, leading to ischaemia. It also blocked photosensitive epilepsies in baboons.^[5]

Other namesCPPene, Midafotel, SDZ EAA 494

ATC code

• none

ExcretionRenal

CAS Number

• 117414-74-1 ^Y

Quick facts Clinical data, Other names ...

Midafotel

Clinical data
Other names	CPPene, Midafotel, SDZ EAA 494
ATC code	none
Pharmacokinetic data
Excretion	Renal
Identifiers
IUPAC name (R)-4-[(E)- 3-phosphonoprop- 2-enyl]piperazine- 2-carboxylic acid
CAS Number	117414-74-1 Y
PubChem CID	6437356
IUPHAR/BPS	4170
ChemSpider	4940497
UNII	7LYU6ZF84G
ChEBI	CHEBI:180900
CompTox Dashboard (EPA)	DTXSID001179674
Chemical and physical data
Formula	C8H15N2O5P
Molar mass	250.191 g·mol−1
3D model (JSmol)	Interactive image
SMILES C1CN(C[C@@H](N1)C(=O)O)C/C=C/P(=O)(O)O
InChI InChI=1S/C8H15N2O5P/c11-8(12)7-6-10(4-2-9-7)3-1-5-16(13,14)15/h1,5,7,9H,2-4,6H2,(H,11,12)(H2,13,14,15)/b5-1+/t7-/m1/s1 Key:VZXMZMJSGLFKQI-ABVWVHJUSA-N
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CPPene had a pharmacokinetic profile suitable for progressing to clinical trials, as it has no toxic byproducts, is excreted exclusively via the renal system, and remains unchanged in the brain.

However, CPPene was removed from clinical trials, as it provided no suitable neuronal protection or beneficial treatment for epilepsy,^[6] and had side effects which led to many patients withdrawing from trials.^[7] A possible explanation for its lack of efficacy in trials is the relatively short therapeutic time window following ischaemic damage and the fact that a small amount of glutamate helps neuronal survival. It is also believed that some "pro-survival" genes are activated by NMDA receptors.