:AP-7 (drug)
{{chembox
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 477236252
| ImageFile=AP-7 2D-Structure.svg
| ImageSize=240px
| Name = AP-7
| PIN=2-Amino-7-phosphonoheptanoic acid
| OtherNames=
|Section1={{Chembox Identifiers
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 3010
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 274440
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C7H16NO5P/c8-6(7(9)10)4-2-1-3-5-14(11,12)13/h6H,1-5,8H2,(H,9,10)(H2,11,12,13)
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = MYDMWESTDPJANS-UHFFFAOYSA-N
| SMILES1 = O=P(O)(O)CCCCCC(C(=O)O)N
| CASNo_Ref = {{cascite|correct|CAS}}
| CASNo=85797-13-3
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = P34K80CUSM
| PubChem=3122
| SMILES=O=P(O)(O)CCCCCC(N)C(=O)O
| InChI=1/C7H16NO5P/c8-6(7(9)10)4-2-1-3-5-14(11,12)13/h6H,1-5,8H2,(H,9,10)(H2,11,12,13)
| MeSHName=
}}
|Section2={{Chembox Properties
| Formula=C7H16NO5P
| MolarMass=225.179 g/mol
| Appearance=
| Density=1.39 g/mL
| MeltingPt=
| BoilingPtC= 480.1
| Solubility=
}}
|Section3={{Chembox Hazards
| MainHazards=
| FlashPt=
| AutoignitionPt =
}}
}}
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.{{cite journal |vauthors=Meldrum B, Millan M, Patel S, de Sarro G | title = Anti-epileptic effects of focal micro-injection of excitatory amino acid antagonists | journal = J. Neural Transm. | volume = 72 | issue = 3 | pages = 191–200 | year = 1988 | pmid = 3047315 | doi = 10.1007/BF01243419 | s2cid = 6216838 }}
AP-7 functions specifically as a NMDA recognition site blocker, in contrast with 7-chlorokynurenate, which acts as a glycine site modulation blocker.{{cite journal | author = Guillemin GJ | title = Quinolinic acid, the inescapable neurotoxin | journal = FEBS J. | volume = 279 | issue = 8 | pages = 1356–65 |date=April 2012 | pmid = 22248144 | doi = 10.1111/j.1742-4658.2012.08485.x | s2cid = 205884904 | doi-access = free }}
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, suggesting that the anxiolytic effect of NMDA antagonists in rats may depend on their action in the DPAG.{{cite journal |vauthors=Guimarães FS, Carobrez AP, De Aguiar JC, Graeff FG | title = Anxiolytic effect in the elevated plus-maze of the NMDA receptor antagonist AP7 microinjected into the dorsal periaqueductal grey | journal = Psychopharmacology | volume = 103 | issue = 1 | pages = 91–4 | year = 1991 | pmid = 1672463 | doi = 10.1007/BF02244080 | s2cid = 6498237 }}
The DPAG of the brain is thought to deal with fear-like defensive behavior via NMDA and glycine B receptors.{{cite journal |vauthors=Carobrez AP, Teixeira KV, Graeff FG | title = Modulation of defensive behavior by periaqueductal gray NMDA/glycine-B receptor | journal = Neurosci Biobehav Rev | volume = 25 | issue = 7–8 | pages = 697–709 |date=December 2001 | pmid = 11801295 | doi = 10.1016/S0149-7634(01)00059-8 | s2cid = 28687622 }} These excitatory glutamate receptors work with the inhibitory GABA receptors to achieve equilibrium in the DPAG of the brain.{{cite journal |vauthors=Car H, Wiśniewski K | title = The effect of baclofen and AP-7 on selected behavior in rats | journal = Pharmacol. Biochem. Behav. | volume = 59 | issue = 3 | pages = 685–9 |date=March 1998 | pmid = 9512072 | doi = 10.1016/S0091-3057(97)00462-0 | s2cid = 37405373 }}
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.{{cite journal |vauthors=Turski L, Klockgether T, Turski WA, Schwarz M, Sontag KH | title = 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 | journal = Brain Res. | volume = 512 | issue = 1 | pages = 125–31 |date=March 1990 | pmid = 2159826 | doi = 10.1016/0006-8993(90)91180-O | s2cid = 37123476 }}
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.{{cite journal |vauthors=Nadlewska A, Car H, Wiśniewska R, Hoły Z, Wiśniewski K | title = Behavioral effects of D-AP7 in rats subjected to experimental hypoxia | journal = Pol J Pharmacol | volume = 55 | issue = 3 | pages = 337–44 | year = 2003 | pmid = 14506312 | url = http://rabbit.if-pan.krakow.pl/pjp/pdf/2003/3_337.pdf }}