A-412,997

A-412,997

Systematic (IUPAC) name
N-(3-methylphenyl)-2-(4-pyridin-2-ylpiperidin-1-yl)acetamide
Clinical data
Pregnancy cat.	?
Legal status	?
Identifiers
ATC code	?
PubChem	CID 10425450
ChemSpider	8600878^Y
ChEMBL	CHEMBL375596^Y
Chemical data
Formula	C₁₉H₂₃N₃O
Mol. mass	309.405 g/mol
SMILES	eMolecules & PubChem
InChI InChI=1S/C19H23N3O/c1-15-5-4-6-17(13-15)21-19(23)14-22-11-8-16(9-12-22)18-7-2-3-10-20-18/h2-7,10,13,16H,8-9,11-12,14H2,1H3,(H,21,23)^Y Key:JFCDMGGMCUKHST-UHFFFAOYSA-N^Y
Y(what is this?) (verify)

A-412,997 is a drug which acts as a dopamine agonist that is used in scientific research. It is the first drug developed that is a highly selective agonist for the D₄ subtype, with significantly improved selectivity over older D₄-preferring compounds such as PD-168,077 and CP-226,269.^[1] In animal tests it improved cognitive performance in rats to a similar extent as methylphenidate, but without producing place preference or other signs of abuse liability.^[2]^[3] Also unlike other dopamine agonists, selective D₄ agonists do not cause side effects such as sedation and nausea, and so might have advantages over older dopamine agonist drugs.^[4]

References

^ Moreland, RB; Patel, M; Hsieh, GC; Wetter, JM; Marsh, K; Brioni, JD (2005). "A-412997 is a selective dopamine D4 receptor agonist in rats". Pharmacology, biochemistry, and behavior 82 (1): 140–7. doi:10.1016/j.pbb.2005.08.001. PMID 16153699.
^ Browman, KE; Curzon, P; Pan, JB; Molesky, AL; Komater, VA; Decker, MW; Brioni, JD; Moreland, RB et al. (2005). "A-412997, a selective dopamine D4 agonist, improves cognitive performance in rats". Pharmacology, biochemistry, and behavior 82 (1): 148–55. doi:10.1016/j.pbb.2005.08.002. PMID 16154186.
^ Woolley ML, Waters KA, Reavill C, Bull S, Lacroix LP, Martyn AJ, Hutcheson DM, Valerio E et al. (December 2008). "Selective dopamine D4 receptor agonist (A-412997) improves cognitive performance and stimulates motor activity without influencing reward-related behaviour in rat". Behavioural Pharmacology 19 (8): 765–76. doi:10.1097/FBP.0b013e32831c3b06. PMID 19020411.
^ Osinski, MA; Uchic, ME; Seifert, T; Shaughnessy, TK; Miller, LN; Nakane, M; Cox, BF; Brioni, JD et al. (2005). "Dopamine D2, but not D4, receptor agonists are emetogenic in ferrets". Pharmacology, biochemistry, and behavior 81 (1): 211–9. doi:10.1016/j.pbb.2005.03.012. PMID 15894081.

Dopaminergics

Receptor ligands

Agonists	Adamantanes: Amantadine • Memantine • Rimantadine; Aminotetralins: 7-OH-DPAT • 8-OH-PBZI • Rotigotine • UH-232; Benzazepines: 6-Br-APB • Fenoldopam • SKF-38,393 • SKF-77,434 • SKF-81,297 • SKF-82,958 • SKF-83,959; Ergolines: Bromocriptine • Cabergoline • Dihydroergocryptine • Lisuride • LSD • Pergolide; Dihydrexidine derivatives: 2-OH-NPA • A-86,929 • Ciladopa • Dihydrexidine • Dinapsoline • Dinoxyline • Doxanthrine; Others: A-68,930 • A-77636 • A-412,997 • ABT-670 • ABT-724 • Aplindore • Apomorphine • Aripiprazole • Bifeprunox • BP-897 • CY-208,243 • Dizocilpine • Etilevodopa • Flibanserin • Ketamine • Melevodopa • Modafinil • Pardoprunox • Phencyclidine • PD-128,907 • PD-168,077 • PF-219,061 • Piribedil • Pramipexole • Propylnorapomorphine • Pukateine • Quinagolide • Quinelorane • Quinpirole • RDS-127 • Ro10-5824 • Ropinirole • Rotigotine • Roxindole • Salvinorin A • SKF-89,145 • Sumanirole • Terguride • Umespirone • WAY-100,635

Antagonists	Typical antipsychotics: Acepromazine • Azaperone • Benperidol • Bromperidol • Clopenthixol • Chlorpromazine • Chlorprothixene • Droperidol • Flupentixol • Fluphenazine • Fluspirilene • Haloperidol • Loxapine • Mesoridazine • Methotrimeprazine • Nemonapride • Penfluridol • Perazine • Periciazine • Perphenazine • Pimozide • Prochlorperazine • Promazine • Sulforidazine • Sulpiride • Sultopride • Thioridazine • Thiothixene • Trifluoperazine • Triflupromazine • Trifluperidol • Zuclopenthixol; Atypical antipsychotics: Amisulpride • Asenapine • Blonanserin • Cariprazine • Carpipramine • Clocapramine • Clorotepine • Clozapine • Gevotroline • Iloperidone • Lurasidone • Melperone • Molindone • Mosapramine • Olanzapine • Paliperidone • Perospirone • Piquindone • Quetiapine • Remoxipride • Risperidone • Sertindole • Tiospirone • Ziprasidone • Zotepine; Antiemetics: AS-8112 • Alizapride • Bromopride • Clebopride • Domperidone • Metoclopramide • Thiethylperazine; Others: Amoxapine • Buspirone • Butaclamol • Ecopipam • EEDQ • Eticlopride • Fananserin • L-745,870 • Nafadotride • Nuciferine • PNU-99,194 • Raclopride • Sarizotan • SB-277,011-A • SCH-23,390 • SKF-83,959 • Sonepiprazole • Spiperone • Spiroxatrine • Stepholidine • Tetrahydropalmatine • Tiapride • UH-232 • Yohimbine

Reuptake inhibitors

Plasmalemmal

DAT inhibitors

Piperazines: DBL-583 • GBR-12,935 • Nefazodone • Vanoxerine; Piperidines: BTCP • Desoxypipradrol • Dextromethylphenidate • Difemetorex • Ethylphenidate • Methylnaphthidate • Methylphenidate • Phencyclidine • Pipradrol; Pyrrolidines: Diphenylprolinol • Methylenedioxypyrovalerone (MDPV) • Naphyrone • Prolintane • Pyrovalerone; Tropanes: β-CPPIT • Altropane • Brasofensine • CFT • Cocaine • Dichloropane • Difluoropine • FE-β-CPPIT • FP-β-CPPIT • Ioflupane (¹²³I) • Iometopane • RTI-112 • RTI-113 • RTI-121 • RTI-126 • RTI-150 • RTI-177 • RTI-229 • RTI-336 • Tenocyclidine • Tesofensine • Troparil • Tropoxane • WF-11 • WF-23 • WF-31 • WF-33; Others: Adrafinil • Armodafinil • Amfonelic acid • Amineptine • Benzatropine (Benztropine) • Bromantane • BTQ • BTS-74,398 • Bupropion (Amfebutamone) • Ciclazindol • Diclofensine • Dimethocaine • Diphenylpyraline • Dizocilpine • DOV-102,677 • DOV-21,947 • DOV-216,303 • Etybenzatropine (Ethylbenztropine) • EXP-561 • Fencamine • Fencamfamine • Fezolamine • GYKI-52,895 • Indatraline • Ketamine • Lefetamine • Levophacetoperane • LR-5182 • Manifaxine • Mazindol • Medifoxamine • Mesocarb • Modafinil • Nefopam • Nomifensine • NS-2359 • O-2172 • Pridefrine • Propylamphetamine • Radafaxine • SEP-225,289 • SEP-227,162 • Sertraline • Sibutramine • Tametraline • Tedatioxetine • Tripelennamine

Vesicular

VMAT inhibitors	Deserpidine • Ibogaine • Reserpine • Tetrabenazine

Releasing agents

Morpholines: Fenbutrazate • Morazone • Phendimetrazine • Phenmetrazine; Oxazolines: 4-Methylaminorex (4-MAR, 4-MAX) • Aminorex • Clominorex • Cyclazodone • Fenozolone • Fluminorex • Pemoline • Thozalinone; Phenethylamines (also amphetamines, cathinones, phentermines, etc): 2-Hydroxyphenethylamine (2-OH-PEA) • 4-CAB • 4-Methylamphetamine (4-MA) • 4-Methylmethamphetamine (4-MMA) • Alfetamine • Amfecloral • Amfepentorex • Amfepramone • Amphetamine (Dextroamphetamine, Levoamphetamine) • Amphetaminil • β-Methylphenethylamine (β-Me-PEA) • Benzodioxolylbutanamine (BDB) • Benzodioxolylhydroxybutanamine (BOH) • Benzphetamine • Buphedrone • Butylone • Cathine • Cathinone • Clobenzorex • Clortermine • D-Deprenyl • Dimethoxyamphetamine (DMA) • Dimethoxymethamphetamine (DMMA) • Dimethylamphetamine • Dimethylcathinone (Dimethylpropion, metamfepramone) • Ethcathinone (Ethylpropion) • Ethylamphetamine • Ethylbenzodioxolylbutanamine (EBDB) • Ethylone • Famprofazone • Fenethylline • Fenproporex • Flephedrone • Fludorex • Furfenorex • Hordenine • Lophophine (Homomyristicylamine) • Mefenorex • Mephedrone • Methamphetamine (Desoxyephedrine, Methedrine; Dextromethamphetamine, Levomethamphetamine) • Methcathinone (Methylpropion) • Methedrone • Methoxymethylenedioxyamphetamine (MMDA) • Methoxymethylenedioxymethamphetamine (MMDMA) • Methylbenzodioxolylbutanamine (MBDB) • Methylenedioxyamphetamine (MDA, tenamfetamine) • Methylenedioxyethylamphetamine (MDEA) • Methylenedioxyhydroxyamphetamine (MDOH) • Methylenedioxymethamphetamine (MDMA) • Methylenedioxymethylphenethylamine (MDMPEA, homarylamine) • Methylenedioxyphenethylamine (MDPEA, homopiperonylamine) • Methylone • Ortetamine • Parabromoamphetamine (PBA) • Parachloroamphetamine (PCA) • Parafluoroamphetamine (PFA) • Parafluoromethamphetamine (PFMA) • Parahydroxyamphetamine (PHA) • Paraiodoamphetamine (PIA) • Paredrine (Norpholedrine, Oxamphetamine) • Phenethylamine (PEA) • Pholedrine • Phenpromethamine • Prenylamine • Propylamphetamine • Tiflorex (Flutiorex) • Tyramine (TRA) • Xylopropamine • Zylofuramine; Piperazines: 2,5-Dimethoxy-4-bromobenzylpiperazine (2C-B-BZP) • Benzylpiperazine (BZP) • Methoxyphenylpiperazine (MeOPP, paraperazine) • Methylbenzylpiperazine (MBZP) • Methylenedioxybenzylpiperazine (MDBZP, piperonylpiperazine); Others: 2-Amino-1,2-dihydronaphthalene (2-ADN) • 2-Aminoindane (2-AI) • 2-Aminotetralin (2-AT) • 4-Benzylpiperidine (4-BP) • 5-IAI • Clofenciclan • Cyclopentamine • Cypenamine • Cyprodenate • Feprosidnine • Gilutensin • Heptaminol • Hexacyclonate • Indanylaminopropane (IAP) • Indanorex • Isometheptene • Methylhexanamine • Naphthylaminopropane (NAP) • Octodrine • Phthalimidopropiophenone • Propylhexedrine (Levopropylhexedrine) • Tuaminoheptane (Tuamine)

Enzyme inhibitors

Anabolism

PAH inhibitors	3,4-Dihydroxystyrene

TH inhibitors	3-Iodotyrosine • Aquayamycin • Bulbocapnine • Metirosine • Oudenone

AAAD/DDC inhibitors	Benserazide • Carbidopa • Genistein • Methyldopa

Catabolism

MAO inhibitors	Nonselective: Benmoxin • Caroxazone • Echinopsidine • Furazolidone • Hydralazine • Indantadol • Iproclozide • Iproniazid • Isocarboxazid • Isoniazid • Linezolid • Mebanazine • Metfendrazine • Nialamide • Octamoxin • Paraxazone • Phenelzine • Pheniprazine • Phenoxypropazine • Pivalylbenzhydrazine • Procarbazine • Safrazine • Tranylcypromine; MAO-A selective: Amiflamine • Bazinaprine • Befloxatone • Befol • Brofaromine • Cimoxatone • Clorgiline • Esuprone • Harmala alkaloids • Methylene Blue • Metralindole • Minaprine • Moclobemide • Pirlindole • Sercloremine • Tetrindole • Toloxatone • Tyrima; MAO-B selective: D-Deprenyl • L-Deprenyl (Selegiline) • Ladostigil • Lazabemide • Milacemide • Pargyline • Rasagiline • Safinamide

COMT inhibitors	Entacapone • Tolcapone

DBH inhibitors	Disulfiram • Dopastin • Fusaric acid • Nepicastat • Tropolone

Others

Precursors	L-Phenylalanine → L-Tyrosine → L-DOPA (Levodopa)

Cofactors	Ferrous iron (Fe²⁺) • Tetrahydrobiopterin • Vitamin B₃ (Niacin, Nicotinamide → NADPH) • Vitamin B₆ (Pyridoxine, Pyridoxamine, Pyridoxal → Pyridoxal phosphate) • Vitamin B₉ (Folic acid → Tetrahydrofolic acid) • Vitamin C (Ascorbic acid) • Zinc (Zn²⁺)

Others	Activity enhancers: Benzofuranylpropylaminopentane (BPAP) • Phenylpropylaminopentane (PPAP); Toxins: Oxidopamine (6-Hydroxydopamine)

List of dopaminergic drugs