Zacopride
Chemical compound
Zacopride is a potent antagonist at the 5-HT3 receptor [1] and an agonist at the 5-HT4 receptor.[2] It has anxiolytic [3] and nootropic effects in animal models,[4] with the (R )-(+)-enantiomer being the more active form.[5] It also has antiemetic [6] and pro-respiratory effects, both reducing sleep apnea [7] and reversing opioid -induced respiratory depression in animal studies.[8] Early animal trials have also revealed that administration of zacopride can reduce preference for and consumption of ethanol.[9]
Zacopride was found to significantly increase aldosterone levels in human subjects for 180 minutes at a dose of 400 micrograms. It is thought to do this by stimulating the 5-HT4 receptors on the adrenal glands. Zacopride also stimulated aldosterone secretion when applied to human adrenal glands in vitro . No significant changes were observed in renin , ACTH , or cortisol levels.[2]
Zacopride has been tested in clinical trials for the treatment of schizophrenia , but was found unsuccessful.[10]
References
^ Smith WW, Sancilio LF, Owera-Atepo JB, Naylor RJ, Lambert L (April 1988). "Zacopride, a potent 5-HT3 antagonist". The Journal of Pharmacy and Pharmacology . 40 (4): 301–2. doi :10.1111/j.2042-7158.1988.tb05253.x . PMID 2900319 . S2CID 32862252 .
^ a b Lefebvre H, Contesse V, Delarue C, Soubrane C, Legrand A, Kuhn JM, et al. (December 1993). "Effect of the serotonin-4 receptor agonist zacopride on aldosterone secretion from the human adrenal cortex: in vivo and in vitro studies". The Journal of Clinical Endocrinology and Metabolism . 77 (6): 1662–6. doi :10.1210/jcem.77.6.8263156 . PMID 8263156 .
^ Costall B, Domeney AM, Gerrard PA, Kelly ME, Naylor RJ (April 1988). "Zacopride: anxiolytic profile in rodent and primate models of anxiety". The Journal of Pharmacy and Pharmacology . 40 (4): 302–5. doi :10.1111/j.2042-7158.1988.tb05254.x . PMID 2900320 . S2CID 1083706 .
^ Fontana DJ, Daniels SE, Eglen RM, Wong EH (March 1996). "Stereoselective effects of (R)- and (S)-zacopride on cognitive performance in a spatial navigation task in rats". Neuropharmacology . 35 (3): 321–7. doi :10.1016/0028-3908(96)00191-8 . PMID 8783207 . S2CID 12818436 .
^ Young R, Johnson DN (August 1991). "Anxiolytic-like activity of R(+)- and S(-)-zacopride in mice". European Journal of Pharmacology . 201 (2–3): 151–5. doi :10.1016/0014-2999(91)90338-Q . PMID 1686755 .
^ Yamakuni H, Nakayama H, Matsui S, Imazumi K, Matsuo M, Mutoh S (May 2006). "Inhibitory effect of zacopride on Cisplatin-induced delayed emesis in ferrets" . Journal of Pharmacological Sciences . 101 (1): 99–102. doi :10.1254/jphs.SCJ05007X . PMID 16651699 .
^ Carley DW, Depoortere H, Radulovacki M (2001). "R-zacopride, a 5-HT3 antagonist/5-HT4 agonist, reduces sleep apneas in rats". Pharmacology, Biochemistry, and Behavior . 69 (1–2): 283–9. doi :10.1016/S0091-3057(01)00535-4 . PMID 11420096 . S2CID 11848748 .
^ Meyer LC, Fuller A, Mitchell D (February 2006). "Zacopride and 8-OH-DPAT reverse opioid-induced respiratory depression and hypoxia but not catatonic immobilization in goats". American Journal of Physiology. Regulatory, Integrative and Comparative Physiology . 290 (2): R405-13. doi :10.1152/ajpregu.00440.2005 . PMID 16166206 . S2CID 224414 .
^ Knapp DJ, Pohorecky LA (April 1992). "Zacopride, a 5-HT3 receptor antagonist, reduces voluntary ethanol consumption in rats". Pharmacology, Biochemistry, and Behavior . 41 (4): 847–50. doi :10.1016/0091-3057(92)90237-A . PMID 1594653 . S2CID 45436887 .
^ Newcomer JW, Faustman WO, Zipursky RB, Csernansky JG (September 1992). "Zacopride in schizophrenia: a single-blind serotonin type 3 antagonist trial". Archives of General Psychiatry . 49 (9): 751–2. doi :10.1001/archpsyc.1992.01820090079013 . PMID 1514881 .
5-HT1
5-HT1A
Agonists: 8-OH-DPAT
Adatanserin
Amphetamine
Antidepressants (e.g., etoperidone , hydroxynefazodone , nefazodone , trazodone , triazoledione , vilazodone , vortioxetine )
Atypical antipsychotics (e.g., aripiprazole , asenapine , brexpiprazole , cariprazine , clozapine , lurasidone , quetiapine , ziprasidone )
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Bay R 1531
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F-11,461
F-12826
F-13714
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F-15063
F-15,599
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LY-293284
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MKC-242
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RU-24,969
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S-15535
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SSR-181507
Sunepitron
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TGBA01AD
U-92,016-A
Urapidil
Vilazodone
Xaliproden
Yohimbine
Antagonists: Atypical antipsychotics (e.g., iloperidone , risperidone , sertindole )
AV965
Beta blockers (e.g., alprenolol , carteolol , cyanopindolol , iodocyanopindolol , isamoltane , oxprenolol , penbutolol , pindobind , pindolol , propranolol , tertatolol )
BMY-7,378
CSP-2503
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Ergolines (e.g., metergoline )
FCE-24379
Flopropione
GR-46611
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Lecozotan
Mefway
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MIN-117 (WF-516)
MPPF
NAN-190
Robalzotan
S-15535
SB-649,915
SDZ 216-525
Spiperone
Spiramide
Spiroxatrine
UH-301
WAY-100135
WAY-100635
Xylamidine
5-HT1B
Agonists: Anpirtoline
CGS-12066A
CP-93129
CP-94253
CP-122,288
CP-135807
Eltoprazine
Ergolines (e.g., bromocriptine , dihydroergotamine , ergotamine , methylergometrine (methylergonovine) , methysergide , pergolide )
mCPP
RU-24,969
Serotonin (5-HT)
Triptans (e.g., avitriptan , donitriptan , eletriptan , sumatriptan , zolmitriptan )
TFMPP
Tryptamines (e.g., 5-BT , 5-CT , 5-MT , DMT )
Vortioxetine
5-HT1D
Agonists: CP-122,288
CP-135807
CP-286601
Ergolines (e.g., bromocriptine , cabergoline , dihydroergotamine , ergotamine , LSD , methysergide )
GR-46611
L-694247
L-772405
mCPP
PNU-109291
PNU-142633
Serotonin (5-HT)
TGBA01AD
Triptans (e.g., almotriptan , avitriptan , donitriptan , eletriptan , frovatriptan , naratriptan , rizatriptan , sumatriptan , zolmitriptan )
Tryptamines (e.g., 5-BT , 5-CT , 5-Et-DMT , 5-MT , 5-(nonyloxy)tryptamine , DMT )
5-HT1E
5-HT1F
5-HT2
5-HT2A
Agonists: 25H/NB series (e.g., 25I-NBF , 25I-NBMD , 25I-NBOH , 25I-NBOMe , 25B-NBOMe , 25C-NBOMe , 25TFM-NBOMe , 2CBCB-NBOMe , 25CN-NBOH , 2CBFly-NBOMe )
2Cs (e.g., 2C-B , 2C-E , 2C-I , 2C-T-2 , 2C-T-7 , 2C-T-21 )
2C-B-FLY
2CB-Ind
5-Methoxytryptamines (5-MeO-DET , 5-MeO-DiPT , 5-MeO-DMT , 5-MeO-DPT , 5-MT )
α-Alkyltryptamines (e.g., 5-Cl-αMT , 5-Fl-αMT , 5-MeO-αET , 5-MeO-αMT , α-Me-5-HT , αET , αMT )
AL-34662
AL-37350A
Bromo-DragonFLY
Dimemebfe
DMBMPP
DOx (e.g., DOB , DOC , DOI , DOM )
Efavirenz
Ergolines (e.g., 1P-LSD , ALD-52 , bromocriptine , cabergoline , ergine (LSA) , ergometrine (ergonovine) , ergotamine , lisuride , LA-SS-Az , LSB , LSD , LSD-Pip , LSH , LSP , methylergometrine (methylergonovine) , pergolide )
Flumexadol
IHCH-7113
Jimscaline
Lorcaserin
MDxx (e.g., MDA (tenamfetamine) , MDMA (midomafetamine) , MDOH , MMDA )
O-4310
Oxaflozane
PHA-57378
PNU-22394
PNU-181731
RH-34
SCHEMBL5334361
Phenethylamines (e.g., lophophine , mescaline )
Piperazines (e.g., BZP , quipazine , TFMPP )
Serotonin (5-HT)
TCB-2
TFMFly
Tryptamines (e.g., 5-BT , 5-CT , bufotenin , DET , DiPT , DMT , DPT , psilocin , psilocybin , tryptamine )
Antagonists: 5-I-R91150
5-MeO-NBpBrT
AC-90179
Adatanserin
Altanserin
Antihistamines (e.g., cyproheptadine , hydroxyzine , ketotifen , perlapine )
AMDA
Atypical antipsychotics (e.g., amperozide , aripiprazole , asenapine , blonanserin , brexpiprazole , carpipramine , clocapramine , clorotepine , clozapine , fluperlapine , gevotroline , iloperidone , lurasidone , melperone , mosapramine , ocaperidone , olanzapine , paliperidone , quetiapine , risperidone , sertindole , zicronapine , ziprasidone , zotepine )
Chlorprothixene
Cinanserin
CSP-2503
Deramciclane
Dotarizine
Eplivanserin
Ergolines (e.g., amesergide , LY-53857 , LY-215,840 , mesulergine , metergoline , methysergide , sergolexole )
Fananserin
Flibanserin
Glemanserin
Irindalone
Ketanserin
KML-010
Landipirdine
LY-393558
mCPP
Medifoxamine
Metitepine (methiothepin)
MIN-117 (WF-516)
Naftidrofuryl
Nantenine
Nelotanserin
Opiranserin (VVZ-149)
Pelanserin
Phenoxybenzamine
Pimavanserin
Pirenperone
Pizotifen
Pruvanserin
Rauwolscine
Ritanserin
Roluperidone
S-14671
Sarpogrelate
Serotonin antagonists and reuptake inhibitors (e.g., etoperidone , hydroxynefazodone , lubazodone , mepiprazole , nefazodone , triazoledione , trazodone )
SR-46349B
TGBA01AD
Teniloxazine
Temanogrel
Tetracyclic antidepressants (e.g., amoxapine , aptazapine , esmirtazapine , maprotiline , mianserin , mirtazapine )
Tricyclic antidepressants (e.g., amitriptyline )
Typical antipsychotics (e.g., chlorpromazine , fluphenazine , haloperidol , loxapine , perphenazine , pimozide , pipamperone , prochlorperazine , setoperone , spiperone , spiramide , thioridazine , thiothixene , trifluoperazine )
Volinanserin
Xylamidine
Yohimbine
5-HT2B
Agonists: 4-Methylaminorex
Aminorex
Amphetamines (e.g., chlorphentermine , cloforex , dexfenfluramine , fenfluramine , levofenfluramine , norfenfluramine )
BW-723C86
DOx (e.g., DOB , DOC , DOI , DOM )
Ergolines (e.g., cabergoline , dihydroergocryptine , dihydroergotamine , ergotamine , methylergometrine (methylergonovine) , methysergide , pergolide )
Lorcaserin
MDxx (e.g., MDA (tenamfetamine) , MDMA (midomafetamine) , MDOH , MMDA )
Piperazines (e.g., TFMPP )
PNU-22394
Ro60-0175
Serotonin (5-HT)
Tryptamines (e.g., 5-BT , 5-CT , 5-MT , α-Me-5-HT , bufotenin , DET , DiPT , DMT , DPT , psilocin , psilocybin , tryptamine )
Antagonists: Agomelatine
Atypical antipsychotics (e.g., amisulpride , aripiprazole , asenapine , brexpiprazole , cariprazine , clozapine , N-desalkylquetiapine (norquetiapine) , N-desmethylclozapine (norclozapine) , olanzapine , pipamperone , quetiapine , risperidone , ziprasidone )
Cyproheptadine
EGIS-7625
Ergolines (e.g., amesergide , bromocriptine , lisuride , LY-53857 , LY-272015 , mesulergine )
Ketanserin
LY-393558
mCPP
Metadoxine
Metitepine (methiothepin)
Pirenperone
Pizotifen
Propranolol
PRX-08066
Rauwolscine
Ritanserin
RS-127445
Sarpogrelate
SB-200646
SB-204741
SB-206553
SB-215505
SB-221284
SB-228357
SDZ SER-082
Tegaserod
Tetracyclic antidepressants (e.g., amoxapine , mianserin , mirtazapine )
Trazodone
Typical antipsychotics (e.g., chlorpromazine )
TIK-301
Yohimbine
5-HT2C
Agonists: 2Cs (e.g., 2C-B , 2C-E , 2C-I , 2C-T-2 , 2C-T-7 , 2C-T-21 )
5-Methoxytryptamines (5-MeO-DET , 5-MeO-DiPT , 5-MeO-DMT , 5-MeO-DPT , 5-MT )
α-Alkyltryptamines (e.g., 5-Cl-αMT , 5-Fl-αMT , 5-MeO-αET , 5-MeO-αMT , α-Me-5-HT , αET , αMT )
A-372159
AL-38022A
Alstonine
CP-809101
Dimemebfe
DOx (e.g., DOB , DOC , DOI , DOM )
Ergolines (e.g., ALD-52 , cabergoline , dihydroergotamine , ergine (LSA) , ergotamine , lisuride , LA-SS-Az , LSB , LSD , LSD-Pip , LSH , LSP , pergolide )
Flumexadol
Lorcaserin
MDxx (e.g., MDA (tenamfetamine) , MDMA (midomafetamine) , MDOH , MMDA )
MK-212
ORG-12962
ORG-37684
Oxaflozane
PHA-57378
Phenethylamines (e.g., lophophine , mescaline )
Piperazines (e.g., aripiprazole , BZP , mCPP , quipazine , TFMPP )
PNU-22394
PNU-181731
Ro60-0175
Ro60-0213
Serotonin (5-HT)
Tryptamines (e.g., 5-BT , 5-CT , bufotenin , DET , DiPT , DMT , DPT , psilocin , psilocybin , tryptamine )
Vabicaserin
WAY-629
WAY-161503
YM-348
Antagonists: Adatanserin
Agomelatine
Atypical antipsychotics (e.g., asenapine , clorotepine , clozapine , fluperlapine , iloperidone , melperone , olanzapine , paliperidone , quetiapine , risperidone , sertindole , ziprasidone , zotepine )
Captodiame
CEPC
Cinanserin
Cyproheptadine
Deramciclane
Desmetramadol
Dotarizine
Eltoprazine
Ergolines (e.g., amesergide , bromocriptine , LY-53857 , LY-215,840 , mesulergine , metergoline , methysergide , sergolexole )
Etoperidone
Fluoxetine
FR-260010
Irindalone
Ketanserin
Ketotifen
Latrepirdine (dimebolin)
Medifoxamine
Metitepine (methiothepin)
Nefazodone
Pirenperone
Pizotifen
Propranolol
Ritanserin
RS-102221
S-14671
SB-200646
SB-206553
SB-221284
SB-228357
SB-242084
SB-243213
SDZ SER-082
Tedatioxetine
Tetracyclic antidepressants (e.g., amoxapine , aptazapine , esmirtazapine , maprotiline , mianserin , mirtazapine )
TIK-301
Tramadol
Trazodone
Tricyclic antidepressants (e.g., amitriptyline , nortriptyline )
Typical antipsychotics (e.g., chlorpromazine , loxapine , pimozide , pipamperone , thioridazine )
Xylamidine
5-HT3 –7
5-HT3
Agonists: Alcohols (e.g., butanol , ethanol (alcohol) , trichloroethanol )
m-CPBG
Phenylbiguanide
Piperazines (e.g., BZP , mCPP , quipazine )
RS-56812
Serotonin (5-HT)
SR-57227
SR-57227A
Tryptamines (e.g., 2-Me-5-HT , 5-CT , bufotenidine (5-HTQ) )
Volatiles/gases (e.g., halothane , isoflurane , toluene , trichloroethane )
YM-31636
Antagonists: Alosetron
Anpirtoline
Arazasetron
AS-8112
Atypical antipsychotics (e.g., clozapine , olanzapine , quetiapine )
Azasetron
Batanopride
Bemesetron (MDL-72222)
Bupropion
Cilansetron
CSP-2503
Dazopride
Dolasetron
Galanolactone
Granisetron
Hydroxybupropion
Lerisetron
Memantine
Ondansetron
Palonosetron
Ramosetron
Renzapride
Ricasetron
Tedatioxetine
Tetracyclic antidepressants (e.g., amoxapine , mianserin , mirtazapine )
Thujone
Tropanserin
Tropisetron
Typical antipsychotics (e.g., loxapine )
Volatiles/gases (e.g., nitrous oxide , sevoflurane , xenon )
Vortioxetine
Zacopride
Zatosetron
5-HT4
5-HT5A
5-HT6
Agonists: Ergolines (e.g., dihydroergocryptine , dihydroergotamine , ergotamine , lisuride , LSD , mesulergine , metergoline , methysergide )
Hypidone
Serotonin (5-HT)
Tryptamines (e.g., 2-Me-5-HT , 5-BT , 5-CT , 5-MT , Bufotenin , E-6801 , E-6837 , EMD-386088 , EMDT , LY-586713 , N-Me-5-HT , ST-1936 , tryptamine )
WAY-181187
WAY-208466
Antagonists: ABT-354
Atypical antipsychotics (e.g., aripiprazole , asenapine , clorotepine , clozapine , fluperlapine , iloperidone , olanzapine , tiospirone )
AVN-101
AVN-211
AVN-322
AVN-397
BGC20-760
BVT-5182
BVT-74316
Cerlapirdine
EGIS-12,233
GW-742457
Idalopirdine
Ketanserin
Landipirdine
Latrepirdine (dimebolin)
Masupirdine
Metitepine (methiothepin)
MS-245
PRX-07034
Ritanserin
Ro 04-6790
Ro 63-0563
SB-258585
SB-271046
SB-357134
SB-399885
SB-742457
Tetracyclic antidepressants (e.g., amoxapine , mianserin )
Tricyclic antidepressants (e.g., amitriptyline , clomipramine , doxepin , nortriptyline )
Typical antipsychotics (e.g., chlorpromazine , loxapine )
5-HT7
Antagonists: Atypical antipsychotics (e.g., amisulpride , aripiprazole , asenapine , brexpiprazole , clorotepine , clozapine , fluperlapine , olanzapine , risperidone , sertindole , tiospirone , ziprasidone , zotepine )
Butaclamol
DR-4485
EGIS-12,233
Ergolines (e.g., 2-Br-LSD (BOL-148) , amesergide , bromocriptine , cabergoline , dihydroergotamine , ergotamine , LY-53857 , LY-215,840 , mesulergine , metergoline , methysergide , sergolexole )
JNJ-18038683
Ketanserin
LY-215,840
Metitepine (methiothepin)
Ritanserin
SB-258719
SB-258741
SB-269970
SB-656104
SB-656104A
SB-691673
SLV-313
SLV-314
Spiperone
SSR-181507
Tetracyclic antidepressants (e.g., amoxapine , maprotiline , mianserin , mirtazapine )
Tricyclic antidepressants (e.g., amitriptyline , clomipramine , imipramine )
Typical antipsychotics (e.g., acetophenazine , chlorpromazine , chlorprothixene , fluphenazine , loxapine , pimozide )
Vortioxetine