Target Information

Target General Infomation
Target ID
T22118
Former ID
TTDS00011
Target Name
Dopamine D1 receptor
Gene Name
DRD1
Synonyms
D(1) dopamine receptor; D(1A) dopamine receptor; DRD1
Target Type
Successful
Disease Allergy [ICD9: 995.3; ICD10: T78.4]
Cocaine addiction [ICD9: 304.2; ICD10: F14.2]
Cognitive disorders [ICD9: 290-294, 294.0, 780.09, 780.9, 780.93; ICD10: F01-F07, F04, F05, R41.3]
Dementia [ICD9: 290-294; ICD10: F01-F07]
Excessive bleeding following childbirth and spontaneous or elective abortion [ICD10: O04]
Glaucoma [ICD9: 365; ICD10: H40-H42]
Hypertension [ICD9: 401; ICD10: I10-I16]
Parkinson's disease [ICD9: 332; ICD10: G20]
Pain [ICD9: 338, 356.0, 356.8,780; ICD10: G64, G90.0, R52, G89]
Psychotic disorders [ICD9: 290-299; ICD10: F20-F29]
Psychiatric disorder [ICD9: 290-319; ICD10: F01-F99]
Substance dependence [ICD10: F10-F19]
Schizophrenia [ICD9: 295; ICD10: F20]
Sexual dysfunction [ICD9: 302.7; ICD10: F52]
Type 2 diabetes [ICD9: 250; ICD10: E11]
Unspecified [ICD code not available]
Function
Dopamine receptor whose activity is mediated by G proteins which activate adenylyl cyclase.
BioChemical Class
GPCR rhodopsin
Target Validation
T22118
UniProt ID
P21728
Sequence
MRTLNTSAMDGTGLVVERDFSVRILTACFLSLLILSTLLGNTLVCAAVIRFRHLRSKVTN
FFVISLAVSDLLVAVLVMPWKAVAEIAGFWPFGSFCNIWVAFDIMCSTASILNLCVISVD
RYWAISSPFRYERKMTPKAAFILISVAWTLSVLISFIPVQLSWHKAKPTSPSDGNATSLA
ETIDNCDSSLSRTYAISSSVISFYIPVAIMIVTYTRIYRIAQKQIRRIAALERAAVHAKN
CQTTTGNGKPVECSQPESSFKMSFKRETKVLKTLSVIMGVFVCCWLPFFILNCILPFCGS
GETQPFCIDSNTFDVFVWFGWANSSLNPIIYAFNADFRKAFSTLLGCYRLCPATNNAIET
VSINNNGAAMFSSHHEPRGSISKECNLVYLIPHAVGSSEDLKKEEAAGIARPLEKLSPAL
SVILDYDTDVSLEKIQPITQNGQHPT
Drugs and Mode of Action
Drug(s) Fenoldopam Drug Info Approved Hypertension [536361], [543348]
Methylergonovine Drug Info Approved Excessive bleeding following childbirth and spontaneous or elective abortion [551871]
Pergolide Drug Info Approved Parkinson's disease [468029], [536285]
Phenyltoloxamine Drug Info Approved Allergy [551871]
Ecopipam Drug Info Phase 3 Cocaine addiction [524163], [540266]
Zicronapine Drug Info Phase 3 Schizophrenia [523357]
DAS-431 IV Drug Info Phase 2 Dementia [551849]
Intranasal apomorphine Drug Info Phase 2 Sexual dysfunction [527086]
Dihydrexidine Drug Info Phase 1/2 Psychotic disorders [532900]
BSF-78438 Drug Info Preclinical Schizophrenia [536463]
D1 agonist D2 antagonist Drug Info Preclinical Schizophrenia [536463]
ADROGOLIDE HYDROCHLORIDE Drug Info Discontinued in Phase 2 Cognitive disorders [546145]
ADX-10061 Drug Info Discontinued in Phase 2 Psychotic disorders [544910]
BAM-1110 Drug Info Discontinued in Phase 2 Parkinson's disease [545888]
CY-208243 Drug Info Discontinued in Phase 2 Pain [528994]
ZELANDOPAM HYDROCHLORIDE Drug Info Discontinued in Phase 2 Hypertension [545254]
Berupipam Drug Info Discontinued in Phase 1 Psychotic disorders [545634]
BTS-73947 Drug Info Discontinued in Phase 1 Psychotic disorders [546424]
Odapipam Drug Info Discontinued in Phase 1 Psychotic disorders [546051]
SDZ-GLC-756 Drug Info Discontinued in Phase 1 Glaucoma [546521]
A 77636 Drug Info Terminated Parkinson's disease [545188]
A-68930 Drug Info Terminated Hypertension [541323], [545191]
A-69024 Drug Info Terminated Psychotic disorders [545268]
BIMG80 Drug Info Terminated Psychotic disorders [546146]
CEE-03-320 Drug Info Terminated Substance dependence [546271]
NNC-22-0031 Drug Info Terminated Psychotic disorders [534327]
Org-10490 Drug Info Terminated Psychotic disorders [551630]
SDZ-PSD-958 Drug Info Terminated Psychiatric disorder [546576]
SKF 38393 Drug Info Terminated Type 2 diabetes [525668], [543309]
SKF-81297 Drug Info Terminated Parkinson's disease [543311], [545672]
Inhibitor (+)-(1R,1'S)-berbamunine hydrochloride Drug Info [551356]
(+)-(1R,1'S)-thaligrisine hydrochloride Drug Info [551356]
(+)-BUTACLAMOL Drug Info [525773]
(+/-)-nantenine Drug Info [530558]
(-)-(1S,1'R)-O,O-dimethylgrisbine hydrochloride Drug Info [551356]
(R)-(+)-coclaurine Drug Info [534656]
(R)-(-)-10-methyl-11-hydroxyaporphine Drug Info [528876]
(R)-(-)-11-hydroxy-N-n-propylnoraporphine Drug Info [529289]
(R)-(-)-2-methoxy-11-hydroxyaporphine Drug Info [529289]
(R)-(-)-2-methoxy-N-npropylnorapomorphine Drug Info [529289]
(R)-(-)-N-ethyl-2-methoxy-11-hydroxynoraporphine Drug Info [529289]
(R)-(-)-N-propyl-2-methoxy-11-hydroxynoraporphine Drug Info [529289]
(R)-11-Amino-2-methoxyaporphine Drug Info [529541]
(R)-2,11-Diaminoaporphine Drug Info [529541]
(R,S)-homoaromaline hydrochloride Drug Info [551356]
(S)-BULBOCAPNINE Drug Info [528616]
(S)APOMORPHINE Drug Info [530342]
(S,S)-oxandrine hydrochloride Drug Info [551356]
1,2,3,7,12,12a-hexahydro-1-aza-pleiaden-5-ol Drug Info [528616]
1,2,3,7,12,12a-hexahydro-1-aza-pleiadene-5,6-diol Drug Info [528616]
1,2-Bis-[R-(-)-apomorphine-2'-oxy]ethane Drug Info [529349]
1-(4-(1H-pyrazol-1-yl)benzyl)-4-phenylpiperazine Drug Info [528099]
1-Aminomethyl-3-cyclohexyl-isochroman-5,6-diol Drug Info [529371]
1-Aminomethyl-3-phenyl-isochroman-5,6-diol Drug Info [530404]
1-Aminomethyl-isochroman-5,6-diol Drug Info [530404]
1-Benzyl-4-(2-ethynyl-pyrrol-1-yl)-piperidine Drug Info [525629]
1-Benzyl-4-(2-iodo-pyrrol-1-yl)-piperidine Drug Info [525629]
1-Benzyl-4-(2-oxazol-5-yl-pyrrol-1-yl)-piperidine Drug Info [525629]
1-Dibenzo[b,f]oxepin-10-yl-4-methyl-piperazine Drug Info [533570]
1-[2-(2-Benzyl-phenoxy)-ethyl]-piperidine Drug Info [527160]
1-[2-(2-Benzyl-phenoxy)-ethyl]-pyrrolidine Drug Info [527160]
1-[3-(2-Benzyl-phenoxy)-propyl]-pyrrolidine Drug Info [527160]
11-Butyryloxy-N-n-propylnoraporphine Drug Info [529686]
11-Heptanoyloxy-N-n-propylnoraporphine Drug Info [529686]
11-Hexanoyloxy-N-n-propylnoraporphine Drug Info [529686]
11-Propionyloxy-N-n-propylnoraporphine Drug Info [529686]
11-valeryloxynoraporphine Drug Info [529686]
2-methoxyapomorphine Drug Info [529349]
2-Methyl-8-phenyl-1,2,3,4-tetrahydro-isoquinoline Drug Info [533578]
2-{[R-(-)-Apomorphine-2'-oxy]ethoxy}-ethanol Drug Info [529349]
3,8-dibromoboldine Drug Info [525759]
3-bromoboldine Drug Info [525759]
3-Chloroboldine Drug Info [525759]
3-Iodoboldine Drug Info [525759]
4-(4-butylpiperidin-1-yl)-1-o-tolylbutan-1-one Drug Info [531079]
4-[2-(2-Benzyl-phenoxy)-ethyl]-morpholine Drug Info [527160]
5-(2-Amino-ethyl)-2-chloro-phenol hydrobromide Drug Info [526782]
6-(2-Amino-ethyl)-biphenyl-2,3,4'-triol Drug Info [533481]
6-(2-Amino-ethyl)-biphenyl-2,3-diol Drug Info [533481]
6-(2-Dipropylamino-ethyl)-biphenyl-2,3,4'-triol Drug Info [533481]
6-(2-Dipropylamino-ethyl)-biphenyl-2,3-diol Drug Info [533481]
9-Aminomethyl-9H-fluorene-2,5,6-triol Drug Info [533481]
9-Aminomethyl-9H-fluorene-3,4-diol Drug Info [533481]
A-70108 Drug Info [530404]
BOLDINE Drug Info [525759]
Dihydrexidine Drug Info [528571]
Etoloxamine Drug Info [527160]
FALCARINDIOL Drug Info [529238]
FLUMEZAPINE Drug Info [533515]
FLUTROLINE Drug Info [533512]
GLAUCINE Drug Info [528616]
IBZM Drug Info [529011]
ISOCLOZAPINE Drug Info [534532]
ISOLOXAPINE Drug Info [533577]
MCL-516 Drug Info [529850]
MELOSMINE Drug Info [528616]
N-(4-Dipropylaminobutyl)-4-biphenylcarboxamide Drug Info [529734]
N-(4-Propylaminobutyl)-4-biphenylcarboxamide Drug Info [529734]
NORSTEPHALAGINE Drug Info [528616]
Phenyltoloxamine Drug Info [527160]
PUKATEINE Drug Info [528616]
QUINPIROLE Drug Info [527714]
R-N-PROPYLNORAPOMORPHINE Drug Info [529289]
Ro-21-7767 Drug Info [533759]
SB-271046 Drug Info [529191]
SCH-12679 Drug Info [534738]
SCH-24518 Drug Info [533416]
SK&F-89626 Drug Info [530341]
STEPHOLIDINE Drug Info [530374]
TEPA (possesses cytotoxic activity) Drug Info [534719]
[R-(-)-Apomorphine-2-yl]-(2'-hydroxy-ethyl)ether Drug Info [529349]
Agonist (+)-ADTN Drug Info [529311]
ADROGOLIDE HYDROCHLORIDE Drug Info [526175], [551871]
CY-208243 Drug Info [533392]
D1 agonist D2 antagonist Drug Info [536463]
DAS-431 IV Drug Info [526175]
Fenoldopam Drug Info [536760]
Intranasal apomorphine Drug Info [534197]
N-propylnorapomorphine Drug Info [529311]
SKF-75670 Drug Info [530363]
SKF-83959 Drug Info [533137]
Modulator A 77636 Drug Info
A-68930 Drug Info [526771]
A-69024 Drug Info [526304]
BAM-1110 Drug Info
BIMG80 Drug Info [534408]
CEE-03-320 Drug Info [546272]
Ecopipam Drug Info
ecopipam (controlled-release, Lesch Nyhan syndrome/Tourette's syndrome/compulsive gambling). Psyadon Pharmaceuticals Drug Info
NNC-22-0031 Drug Info [534327]
Org-10490 Drug Info [556264]
Pergolide Drug Info [556264]
SDZ-GLC-756 Drug Info [534322]
SDZ-PSD-958 Drug Info [534179]
SKF 38393 Drug Info [525668]
SKF-81297 Drug Info [533794]
Zicronapine Drug Info [549861]
Antagonist ADX-10061 Drug Info [544911]
Berupipam Drug Info [533594]
BTS-73947 Drug Info [546425], [551871]
Methylergonovine Drug Info [536092]
Odapipam Drug Info [525486]
SCH-23390 Drug Info [537186]
SKF-83556 Drug Info [529311]
ZELANDOPAM HYDROCHLORIDE Drug Info [527452], [551871]
[125I]SCH23982 Drug Info [531411]
[3H]SCH-23390 Drug Info [531521]
Binder BSF-78438 Drug Info [536463]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway Calcium signaling pathway
cAMP signaling pathway
Neuroactive ligand-receptor interaction
Gap junction
Dopaminergic synapse
Parkinson&#039
s disease
Cocaine addiction
Amphetamine addiction
Morphine addiction
Alcoholism
PANTHER Pathway Dopamine receptor mediated signaling pathway
PathWhiz Pathway Dopamine Activation of Neurological Reward System
Reactome Dopamine receptors
G alpha (s) signalling events
WikiPathways Hypothetical Network for Drug Addiction
Monoamine GPCRs
GPCRs, Class A Rhodopsin-like
Genes and (Common) Pathways Underlying Drug Addiction
GPCR ligand binding
GPCR downstream signaling
References
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Ref 523357ClinicalTrials.gov (NCT01295372) Safety and Efficacy of Zicronapine in Patients With Schizophrenia. U.S. National Institutes of Health.
Ref 524163ClinicalTrials.gov (NCT01751802) Ecopipam Treatment of Self-Injurious Behavior in Subjects With Lesch-Nyhan Disease. U.S. National Institutes of Health.
Ref 525668The D1 dopamine receptor agonist SKF-38393 stimulates the release of glutamate in the hippocampus. Neuroscience. 1999;94(4):1063-70.
Ref 527086Intranasal apomorphine. Nastech Pharmaceutical. IDrugs. 2004 May;7(5):483-8.
Ref 528994Decrease of behavioral and biochemical denervation supersensitivity of rat striatum by nigral transplants. Neuroscience. 1991;44(1):75-83.
Ref 532900Effects of the D1 dopamine receptor agonist dihydrexidine (DAR-0100A) on working memory in schizotypal personality disorder. Neuropsychopharmacology. 2015 Jan;40(2):446-53.
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Ref 541323(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6077).
Ref 543309(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 935).
Ref 543311(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 938).
Ref 543348(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 985).
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Ref 546271Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800007189)
Ref 546424Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800008043)
Ref 546521Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800008736)
Ref 546576Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800009027)
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Ref 525759J Nat Prod. 2000 Apr;63(4):480-4.Halogenated boldine derivatives with enhanced monoamine receptor selectivity.
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Ref 526782J Med Chem. 1992 Nov 13;35(23):4408-14.Synthesis and pharmacological characterization of 2-(4-chloro-3-hydroxyphenyl)ethylamine and N,N-dialkyl derivatives as dopamine receptor ligands.
Ref 527160J Med Chem. 2004 Aug 12;47(17):4155-8.Dopamine/serotonin receptor ligands. 9. Oxygen-containing midsized heterocyclic ring systems and nonrigidized analogues. A step toward dopamine D5 receptor selectivity.
Ref 527452Effect of zelandopam, a dopamine D1-like receptor agonist, in puromycin aminonucleoside nephrosis rats. Eur J Pharmacol. 2005 Mar 7;510(1-2):121-6.
Ref 527714J Med Chem. 2005 Sep 8;48(18):5771-9.Pharmacophore-guided drug discovery investigations leading to bioactive 5-aminotetrahydropyrazolopyridines. Implications for the binding mode of heterocyclic dopamine D3 receptor agonists.
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Ref 528571J Med Chem. 2006 Nov 16;49(23):6848-57.trans-2,3-dihydroxy-6a,7,8,12b-tetrahydro-6H-chromeno[3,4-c]isoquinoline: synthesis, resolution, and preliminary pharmacological characterization of a new dopamine D1 receptor full agonist.
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Ref 528876Bioorg Med Chem Lett. 2007 Aug 1;17(15):4128-30. Epub 2007 May 23.R-(-)-N-alkyl-11-hydroxy-10-hydroxymethyl- and 10-methyl-aporphines as 5-HT1A receptor ligands.
Ref 529011Bioorg Med Chem. 2007 Nov 1;15(21):6819-29. Epub 2007 Aug 19.In vitro affinities of various halogenated benzamide derivatives as potential radioligands for non-invasive quantification of D(2)-like dopamine receptors.
Ref 529191Bioorg Med Chem Lett. 2008 Jan 15;18(2):738-43. Epub 2007 Nov 17.Discovery of 3-aryl-3-methyl-1H-quinoline-2,4-diones as a new class of selective 5-HT6 receptor antagonists.
Ref 529238Bioorg Med Chem. 2008 Mar 15;16(6):3218-23. Epub 2007 Dec 31.Novel coumarin glycoside and phenethyl vanillate from Notopterygium forbesii and their binding affinities for opioid and dopamine receptors.
Ref 529289J Med Chem. 2008 Feb 28;51(4):983-7. Epub 2008 Feb 6.Synthesis and dopamine receptor affinities of N-alkyl-11-hydroxy-2-methoxynoraporphines: N-alkyl substituents determine D1 versus D2 receptor selectivity.
Ref 529311Cloning of the gene for a human dopamine D5 receptor with higher affinity for dopamine than D1. Nature. 1991 Apr 18;350(6319):614-9.
Ref 529349Bioorg Med Chem. 2008 Apr 15;16(8):4563-8. Epub 2008 Feb 15.Synthesis and neuropharmacological characterization of 2-O-substituted apomorphines.
Ref 529371J Med Chem. 1991 Oct;34(10):2946-53.Synthesis and pharmacological evaluation of 1-(aminomethyl)-3,4-dihydro-5-hydroxy-1H-2-benzopyrans as dopamine D1 selective ligands.
Ref 529541Bioorg Med Chem. 2008 Jul 15;16(14):6675-81. Epub 2008 Jun 5.Synthesis and pharmacological investigation of novel 2-aminothiazole-privileged aporphines.
Ref 529686Bioorg Med Chem. 2008 Sep 15;16(18):8335-8. Epub 2008 Aug 28.N-Propylnoraporphin-11-O-yl carboxylic esters as potent dopamine D(2) and serotonin 5-HT(1A) receptor dual ligands.
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Ref 529850Bioorg Med Chem Lett. 2009 Jan 1;19(1):51-3. Epub 2008 Nov 13.Synthesis and neuropharmacological evaluation of esters of R(-)-N-alkyl-11-hydroxy-2-methoxynoraporphines.
Ref 530341J Med Chem. 1990 Jun;33(6):1756-64.trans-10,11-dihydroxy-5,6,6a,7,8,12b-hexahydrobenzo[a]phenanthridine: a highly potent selective dopamine D1 full agonist.
Ref 530342J Med Chem. 1990 Jun;33(6):1800-5.Synthesis and dopamine receptor affinities of enantiomers of 2-substituted apomorphines and their N-n-propyl analogues.
Ref 530363Dopamine receptor agonists: selectivity and dopamine D1 receptor efficacy. Eur J Pharmacol. 1990 Jun 12;188(6):335-47.
Ref 530374Bioorg Med Chem. 2009 Oct 1;17(19):6898-907. Epub 2009 Aug 20.Dibenzazecine scaffold rebuilding--is the flexibility always essential for high dopamine receptor affinities?.
Ref 530404J Med Chem. 1990 Nov;33(11):2948-50.(1R,3S)-1-(aminomethyl)-3,4-dihydro-5,6-dihydroxy-3-phenyl-1H-2-benzopyran: a potent and selective D1 agonist.
Ref 530558Bioorg Med Chem Lett. 2010 Jan 15;20(2):628-31. Epub 2009 Nov 20.Synthetic studies and pharmacological evaluations on the MDMA ('Ecstasy') antagonist nantenine.
Ref 531079J Med Chem. 2010 Sep 9;53(17):6386-97.Discovery of N-{1-[3-(3-oxo-2,3-dihydrobenzo[1,4]oxazin-4-yl)propyl]piperidin-4-yl}-2-phenylacetamide (Lu AE51090): an allosteric muscarinic M1 receptor agonist with unprecedented selectivity and procognitive potential.
Ref 531411Molecular cloning and expression of the gene for a human D1 dopamine receptor. Nature. 1990 Sep 6;347(6288):72-6.
Ref 531521Cloning and expression of human and rat D1 dopamine receptors. Nature. 1990 Sep 6;347(6288):76-80.
Ref 533137Identification of G protein-biased agonists that fail to recruit beta-arrestin or promote internalization of the D1 dopamine receptor. ACS Chem Neurosci. 2015 Apr 15;6(4):681-92.
Ref 533392The D-1 dopamine receptor partial agonist, CY 208-243, exhibits antiparkinsonian activity in the MPTP-treated marmoset. Eur J Pharmacol. 1988 Nov 1;156(2):197-206.
Ref 533416J Med Chem. 1988 Oct;31(10):1941-6.Synthesis and pharmacological characterization of 1-phenyl-, 4-phenyl-, and 1-benzyl-1,2,3,4-tetrahydroisoquinolines as dopamine receptor ligands.
Ref 533481J Med Chem. 1986 Oct;29(10):1904-12.Synthesis and dopaminergic binding of 2-aryldopamine analogues: phenethylamines, 3-benzazepines, and 9-(aminomethyl)fluorenes.
Ref 533512J Med Chem. 1980 Jun;23(6):635-43.Neuroleptic activity in 5-aryltetrahydro-gamma-carbolines.
Ref 533515J Med Chem. 1982 Oct;25(10):1133-40.Effects of conformationally restricted 4-piperazinyl-10H-thienobenzodiazepine neuroleptics on central dopaminergic and cholinergic systems.
Ref 533570J Med Chem. 1982 Jul;25(7):855-8.Affinity of 10-(4-methylpiperazino)dibenz[b,f]oxepins for clozapine and spiroperidol binding sites in rat brain.
Ref 533577J Med Chem. 1981 Sep;24(9):1021-6.Synthesis of clozapine analogues and their affinity for clozapine and spiroperidol binding sites in rat brain.
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