AMPA receptors ampakines

The ampakines are a group of compounds that facilitate transmission by stimulating the AMPA glutamate receptors (see p. 58). The AMPA receptor is believed to play a major role in long-term potentiation, a physiological process that is important in memory formation. Experimental studies in aged rats have already shown that the ampakines can reverse age-associated memory loss but their activity in Alzheimer s patients has yet to be determined. 

Because AMPA receptors function in concert with NMDA receptors, they have been proposed as alternative therapeutic targets in schizophrenia. AMPAkines function as positive allosteric modulators of AMPA receptor-mediated neurotransmission, and facilitate learning and memory in both human (Ingvar et al., 1997) and animal (Hampson et al., 1998) models. Further, these drugs act synergistically with antipsycho-tics to reverse amphetamine-induced hyperactivity (Johnson et al., 1999). 

The ionotropic glutamic acid or-amino-B-hydroxy-.S-mcthyl-4-i.soxazolc propionic acid (AMPA) receptors are activate by brain-penetrating ampakines. There are suggestions that thc.se agents exert. some antipsychotic actions by increasing glutaminergic activity. 

Ampakines are drugs that potentiate currents mediated by AMPA-type glutamate receptors. In behavioral tests, ampakines are effective in correcting behaviors in various animal models of schizophrenia and depression. They protect neurons against neurotoxic insults, in part by mobilizing growth factors such as brain-derived neurotrophic factor (BDNF). 

Conversely, a new line of inquiry examined glutamatergic activity, not as a blocker of neurotransmission but as an agonist of AMPA type receptors. A new class of compounds, called ampakines, act as long-term boosters of the learning process, Aniracetam [206] is considered as the major product in this series. It improves performance in all classical behavioural tests in animal models. The question which has to be answered is whether these compounds simply have symptomatic effects on memory processes or whether they have complementary properties such as inhibition of cell death [207], Furthermore, certain compounds currently classed as ampakines such as oxiracetam and piracetam have not been shown to be effective in Alzheimer s disease. Others, such as nefiracetam (12) are in the animal experimentation stage and appear to be promising because of their impact on the neuronal cell adhesion molecules (NCAM) [208] and their effect on synapse plasticity. 

---