Chemistry:Midafotel
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| Other names | CPPene, Midafotel, SDZ EAA 494 |
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| Excretion | Renal |
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| Formula | C8H15N2O5P |
| Molar mass | 250.191 g·mol−1 |
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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]
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.
See also
References
- ↑ "D-CPP-ene (SDZ EAA 494), a potent and competitive N-methyl-D-aspartate (NMDA) antagonist: effect on spontaneous activity and NMDA-induced depolarizations in the rat neocortical slice preparation, compared with other CPP derivatives and MK-801". Neuroscience Letters 113 (3): 315–21. June 1990. doi:10.1016/0304-3940(90)90604-8. PMID 2166255.
- ↑ "Focal ischemic damage is reduced by CPP-ene studies in two animal models". Stroke 21 (11 Suppl): III32-6. November 1990. PMID 2146780.
- ↑ "Prolongation of morphine analgesia by competitive NMDA receptor antagonist D-CPPene (SDZ EAA 494) in rats". European Journal of Pharmacology 351 (3): 299–305. June 1998. doi:10.1016/s0014-2999(98)00324-0. PMID 9721021.
- ↑ "The pharmacology of SDZ EAA 494, a competitive NMDA antagonist". Neurochemistry International 25 (6): 583–600. December 1994. doi:10.1016/0197-0186(94)90157-0. PMID 7894335.
- ↑ "Anticonvulsant activity of the NMDA antagonists, D(-)4-(3-phosphonopropyl) piperazine-2-carboxylic acid (D-CPP) and D(-)(E)-4-(3-phosphonoprop-2-enyl) piperazine-2-carboxylic acid (D-CPPene) in a rodent and a primate model of reflex epilepsy". Epilepsy Research 7 (1): 3–10. 1990. doi:10.1016/0920-1211(90)90049-2. PMID 2292244.
- ↑ "The excitatory amino acid antagonist D-CPP-ene (SDZ EAA-494) in patients with epilepsy". Epilepsy Research 16 (2): 165–74. October 1993. doi:10.1016/0920-1211(93)90031-2. PMID 8269915.
- ↑ "Effects of the novel NMDA-receptor antagonist SDZ EAA 494 on memory and attention in humans". Psychopharmacology 124 (3): 261–6. April 1996. doi:10.1007/bf02246666. PMID 8740048.
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