AP-7 (drug) explained

AP-7 is a selective NMDA receptor (NMDAR) antagonist that competitively inhibits the glutamate binding site and thus activation of NMDAR. It has anticonvulsant effects.^[1]

AP-7 functions specifically as a NMDA recognition site blocker, in contrast with 7-chlorokynurenate, which acts as a glycine site modulation blocker.^[2]

Animal studies

AP-7 injected directly into the dorsal periaqueductal grey (DPAG) of rats produced an anxiolytic effect, whereas direct injection outside of the DPAG did not elicit anxiolytic effects. This suggests that a portion of systemically taken NMDA antagonist's anxiolytic effects comes from the DPAG region of the brain, at least in rats.^[3]

The DPAG of the brain is thought to deal with fear-like defensive behavior via NMDA and glycine B receptors.^[4] These excitatory glutamate receptors work with the inhibitory GABA receptors to achieve equilibrium in the DPAG of the brain.^[5]

AP-7 has been known to cause muscle rigidity and catalepsy in rats following bilateral microinjections (0.02-0.5 nmol) into the globus pallidus and ventral-posterior portions of the caudate-putamen.^[6]

The optically pure D-(−)-2-amino-7-phosphonoheptanoic acid [D-AP7], has also been examined. In groups of hypoxia-treated rats, D-AP7 enhanced motility, exhibited anxiogenic-like effect and impaired consolidation in passive avoidance. Both AP-7 and D-AP7 function as potent, specific antagonists of the NMDA receptor.^[7]

See also

• APV (drug)

Notes and References

1. Meldrum B, Millan M, Patel S, de Sarro G . Anti-epileptic effects of focal micro-injection of excitatory amino acid antagonists . J. Neural Transm. . 72 . 3 . 191–200 . 1988 . 3047315 . 10.1007/BF01243419 . 6216838 .
2. Guillemin GJ . Quinolinic acid, the inescapable neurotoxin . FEBS J. . 279 . 8 . 1356–65 . April 2012 . 22248144 . 10.1111/j.1742-4658.2012.08485.x . 205884904 . free .
3. Guimarães FS, Carobrez AP, De Aguiar JC, Graeff FG . Anxiolytic effect in the elevated plus-maze of the NMDA receptor antagonist AP7 microinjected into the dorsal periaqueductal grey . Psychopharmacology . 103 . 1 . 91–4 . 1991 . 1672463 . 10.1007/BF02244080 . 6498237 .
4. Carobrez AP, Teixeira KV, Graeff FG . Modulation of defensive behavior by periaqueductal gray NMDA/glycine-B receptor . Neurosci Biobehav Rev . 25 . 7–8 . 697–709 . December 2001 . 11801295 . 10.1016/S0149-7634(01)00059-8 . 28687622 .
5. Car H, Wiśniewski K . The effect of baclofen and AP-7 on selected behavior in rats . Pharmacol. Biochem. Behav. . 59 . 3 . 685–9 . March 1998 . 9512072 . 10.1016/S0091-3057(97)00462-0 . 37405373 .
6. Turski L, Klockgether T, Turski WA, Schwarz M, Sontag KH . Blockade of excitatory neurotransmission in the globus pallidus induces rigidity and akinesia in the rat: implications for excitatory neurotransmission in pathogenesis of Parkinson's diseases . Brain Res. . 512 . 1 . 125–31 . March 1990 . 2159826 . 10.1016/0006-8993(90)91180-O . 37123476 .
7. Nadlewska A, Car H, Wiśniewska R, Hoły Z, Wiśniewski K . Behavioral effects of D-AP7 in rats subjected to experimental hypoxia . Pol J Pharmacol . 55 . 3 . 337–44 . 2003 . 14506312 .