Isonipecotic acid

{{cs1 config|name-list-style=vanc|display-authors=6}} {{Infobox drug | Verifiedfields = changed | Watchedfields = changed | verifiedrevid = 381938730 | drug_name = | image = Isonipecotic-acid-2D-skeletal.svg | image_class = skin-invert-image | width = 115px | caption = | image2 = Isonipecotic-acid-3D-balls.png | image_class2 = bg-transparent | width2 = 115px | caption2 =

<!-- Clinical data --> | pronounce = | tradename = | Drugs.com = | MedlinePlus = | licence_CA = | licence_EU = | DailyMedID = | licence_US = | pregnancy_AU = | pregnancy_category = | dependency_liability = | addiction_liability = | routes_of_administration = | class = GABA_A receptor partial agonist | ATC_prefix = None | ATC_suffix =

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<!-- Identifiers --> | CAS_number_Ref = {{cascite|correct|CAS}} | CAS_number = 498-94-2 | CAS_supplemental = | PubChem = 3773 | PubChemSubstance = | IUPHAR_ligand = 4227 | DrugBank = | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 3641 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = M5TZP1RWIE | KEGG = | ChEBI = | ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL = 279998 | NIAID_ChemDB = | PDB_ligand = | synonyms = Piperidine-4-carboxylic acid; P4C; 4-Piperidinecarboxylic acid; Hexahydroisonicotinic acid; 4-Carboxypiperidine

<!-- Chemical data --> | IUPAC_name = piperidine-4-carboxylic acid | C=6 | H=11 | N=1 | O=2 | SMILES = C1CNCCC1C(=O)O | StdInChI_Ref = {{stdinchicite|changed|chemspider}} | StdInChI = 1S/C6H11NO2/c8-6(9)5-1-3-7-4-2-5/h5,7H,1-4H2,(H,8,9) | StdInChIKey_Ref = {{stdinchicite|changed|chemspider}} | StdInChIKey = SRJOCJYGOFTFLH-UHFFFAOYSA-N }}

'''Isonipecotic acid''', also known as '''piperidine-4-carboxylic acid''' ('''P4C'''), is a conformationally constrained derivative of γ-aminobutyric acid (GABA) and a moderately potent GABA_A receptor partial agonist.<ref name="Kerr_1992">{{cite journal | vauthors = Kerr DI, Ong J | title = GABA agonists and antagonists | journal = Medicinal Research Reviews | volume = 12 | issue = 6 | pages = 593–636 | date = November 1992 | pmid = 1331633 | doi = 10.1002/med.2610120604 }}</ref><ref name="Frlund_2002">{{cite journal | vauthors = Frølund B, Ebert B, Kristiansen U, Liljefors T, Krogsgaard-Larsen P | title = GABA(A) receptor ligands and their therapeutic potentials | journal = Current Topics in Medicinal Chemistry | volume = 2 | issue = 8 | pages = 817–832 | date = August 2002 | pmid = 12171573 | doi = 10.2174/1568026023393525 }}</ref><ref name="Mortensen_2004">{{cite journal | vauthors = Mortensen M, Kristiansen U, Ebert B, Frølund B, Krogsgaard-Larsen P, Smart TG | title = Activation of single heteromeric GABA(A) receptor ion channels by full and partial agonists | journal = The Journal of Physiology | volume = 557 | issue = Pt 2 | pages = 389–413 | date = June 2004 | pmid = 14990676 | pmc = 1665090 | doi = 10.1113/jphysiol.2003.054734 }}</ref> It consists of a piperidine ring with a carboxylic acid moiety in the ''iso'' position.<ref name="Kerr_1992" /> The drug showed moderate-efficacy partial agonism of α₁, α₂, α₃, and α₅ subunit-containing GABA_A receptors ({{Abbrlink|E_max|maximal efficacy}} = 46–57%), but showed full or near-full agonism of α₄ and α₆ subunit-containing GABA_A receptors ({{Abbr|E_max|maximal efficacy}} = 83–104%).<ref name="Frlund_2002" /> Isonipecotic acid is unable to cross the blood–brain barrier.<ref name="Crider_1982">{{cite journal | vauthors = Crider AM, Tita TT, Wood JD, Hinko CN | title = Esters of nipecotic and isonipecotic acids as potential anticonvulsants | journal = Journal of Pharmaceutical Sciences | volume = 71 | issue = 11 | pages = 1214–1219 | date = November 1982 | pmid = 7175711 | doi = 10.1002/jps.2600711108 | bibcode = 1982JPhmS..71.1214M | quote = Isonipecotic acid (Ib) was shown to be a potent and specific y-aminobutyric acid agonist in the [3H]y-aminobutyric acid-binding assay procedure (13,14). As in the case of nipecotic acid, isonipecotic acid was also too polar to penetrate the blood-brain barrier. }}</ref> It was first described in the scientific literature by at least 1944<ref name="Wibaut_1944">{{cite journal | vauthors = Wibaut JP | title = The preparation of pyridine-4-carboxylic acid and of piperidine-4-carboxylic acid by catalytic reduction of 2,6-dichloropyridine-4-carboxylic acid | journal = Recueil des Travaux Chimiques des Pays-Bas | volume = 63 | issue = 7 | pages = 141–146 | date = 1944 | doi = 10.1002/recl.19440630704 | issn = 0165-0513 | url = https://onlinelibrary.wiley.com/doi/10.1002/recl.19440630704 | access-date = 6 October 2025 | url-access = subscription }}</ref> and was identified as a GABA_A receptor agonist by 1978.<ref name="Bowery_1978">{{cite journal | vauthors = Bowery NG, Collins JF, Hudson AL, Neal MJ | title = Isoguvacine, isonipecotic acid, muscimol and N-methyl isoguvacine on the GABA receptor in rat sympathetic ganglia | journal = Experientia | volume = 34 | issue = 9 | pages = 1193–1195 | date = September 1978 | pmid = 214333 | doi = 10.1007/BF01922953 }}</ref>

== See also == * Piperidine-4-sulfonic acid (P4S) * Isoguvacine * Gaboxadol * Muscimol * Nipecotic acid

== References == {{Reflist}}

{{GABA receptor modulators}} {{Glycine receptor modulators}}

Category:4-Piperidinyl compounds Category:Biased ligands Category:Carboxylic acids Category:GABA analogues Category:GABAA receptor agonists Category:GABAA-rho receptor antagonists Category:Glycine receptor antagonists Category:Peripherally selective drugs Category:Sedatives

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