Medication used to treat seizures
Fenfluramine , sold under the brand name Fintepla , is a
serotonergic medication used for the treatment of
seizures associated with
Dravet syndrome and
Lennox–Gastaut syndrome .
[6]
[7]
[3] It was formerly used as an
appetite suppressant in the treatment of
obesity , but was discontinued for this use due to
cardiovascular
toxicity before being repurposed for new indications.
[8]
[9] Fenfluramine was used for
weight loss both alone under the brand name Pondimin and
in combination with
phentermine commonly known as
fen-phen .
[8]
[10]
[11]
Side effects of fenfluramine in people treated for seizures include
decreased appetite ,
somnolence ,
sedation ,
lethargy ,
diarrhea ,
constipation ,
abnormal echocardiogram ,
fatigue ,
malaise ,
asthenia ,
ataxia ,
balance disorder ,
gait disturbance ,
increased blood pressure ,
drooling ,
excessive salivation ,
fever ,
upper respiratory tract infection ,
vomiting ,
appetite loss ,
weight loss ,
falls , and
status epilepticus .
[6] Fenfluramine acts as a
serotonin releasing agent ,
agonist of the
serotonin
5-HT2 receptors , and
σ1 receptor
positive modulator .
[12]
[13]
[14] Its
mechanism of action in the treatment of seizures is unknown,
[6] but may involve increased activation of certain serotonin receptors and the σ1 receptor.
[13]
[9]
[15]
Fenfluramine was developed in the early 1960s and was first introduced for medical use as an appetite suppressant in
France in 1963 followed by approval in the
United States in 1973.
[8] In the 1990s, fenfluramine came to be associated with cardiovascular toxicity, and because of this, was
withdrawn from the United States market in 1997.
[8]
[16] Subsequently, it was repurposed for the treatment of seizures and was reintroduced in the United States and the
European Union in 2020.
[7]
[3]
[9] Fenfluramine was previously a
schedule IV
controlled substance in the United States.
[7] However, the substance has since no-longer been subject to control pursuant to rule-making issued on 23 December 2022.
[17]
Medical uses
Seizures
Fenfluramine is indicated for the treatment of seizures associated with
Dravet syndrome and
Lennox–Gastaut syndrome in people age two and older.
[6]
[7]
[3]
Dravet syndrome is a life-threatening, rare and chronic form of
epilepsy .
[7] It is often characterized by severe and unrelenting seizures despite medical treatment.
[7]
Obesity
Fenfluramine was formerly used as an
appetite suppressant in the treatment of
obesity , but was
withdrawn for this use due to cardiovascular toxicity.
[8]
Adverse effects
The most common adverse reactions in people with seizures include decreased appetite; drowsiness, sedation and lethargy; diarrhea; constipation; abnormal echocardiogram; fatigue or lack of energy; ataxia (lack of coordination), balance disorder, gait disturbance (trouble with walking); increased blood pressure; drooling, salivary hypersecretion (saliva overproduction); pyrexia (fever); upper respiratory tract infection; vomiting; decreased weight; risk of falls; and status epilepticus.
[7]
The U.S.
Food and Drug Administration (FDA) fenfluramine labeling includes a boxed warning stating the drug is associated with valvular heart disease (VHD) and pulmonary arterial hypertension (PAH).
[7] Because of the risks of VHD and PAH, fenfluramine is available only through a restricted drug distribution program, under a risk evaluation and mitigation strategy (REMS).
[7] The fenfluramine REMS requires health care professionals who prescribe fenfluramine and pharmacies that dispense fenfluramine to be specially certified in the fenfluramine REMS and that patients be enrolled in the REMS.
[7] As part of the REMS requirements, prescribers and patients must adhere to the required cardiac monitoring with echocardiograms to receive fenfluramine.
[7]
At higher therapeutic doses,
headache ,
diarrhea ,
dizziness ,
dry mouth ,
erectile dysfunction ,
anxiety ,
insomnia ,
irritability ,
lethargy , and
CNS stimulation have been reported with fenfluramine.
[5]
There have been reports associating chronic fenfluramine treatment with
emotional instability ,
cognitive deficits ,
depression ,
psychosis , exacerbation of pre-existing psychosis (
schizophrenia ), and
sleep disturbances .
[5]
[18] It has been suggested that some of these effects may be mediated by
serotonergic
neurotoxicity /depletion of serotonin with chronic administration and/or activation of serotonin
5-HT2A receptors .
[18]
[19]
[20]
[21]
Heart valve disease
The distinctive valvular abnormality seen with fenfluramine is a thickening of the leaflet and
chordae tendineae . One mechanism used to explain this phenomenon involves heart valve serotonin receptors, which are thought to help regulate growth. Since fenfluramine and its active metabolite
norfenfluramine stimulate serotonin receptors, this may have led to the valvular abnormalities found in patients using fenfluramine. In particular norfenfluramine is a potent inhibitor of the re-uptake of 5-HT into nerve terminals.
[22] Fenfluramine and its active metabolite norfenfluramine affect the
5-HT2B receptors , which are plentiful in human cardiac valves. The suggested mechanism by which fenfluramine causes damage is through over or inappropriate stimulation of these receptors leading to inappropriate valve cell division. Supporting this idea is the fact that this valve abnormality has also occurred in patients using other drugs that act on 5-HT2B receptors.
[23]
[24]
According to a study of 5,743 former users conducted by a plaintiff's expert cardiologist, damage to the heart valve continued long after stopping the medication.
[25] Of the users tested, 20% of women, and 12% of men were affected. For all ex-users, there was a 7-fold increase of chances of needing surgery for faulty heart valves caused by the drug.
[25]
Overdose
In
overdose , fenfluramine can cause
serotonin syndrome and rapidly result in death.
[8]
[26]
Pharmacology
Pharmacodynamics
Fenfluramine acts primarily as a
serotonin releasing agent .
[27]
[28] It increases the level of
serotonin , a
neurotransmitter that regulates mood, appetite and other functions.
[27]
[28] Fenfluramine
causes the release of serotonin by disrupting
vesicular storage of the neurotransmitter, and reversing serotonin
transporter function.
[29] The drug also acts as a
norepinephrine releasing agent to a lesser extent, particularly via its
active metabolite
norfenfluramine .
[27]
[28] At high concentrations, norfenfluramine, though not fenfluramine, also acts as a
dopamine releasing agent , and so fenfluramine may do this at very high doses as well.
[27]
[28] In addition to monoamine release, while fenfluramine binds only very weakly to the serotonin
5-HT2 receptors , norfenfluramine binds to and activates the serotonin
5-HT2B and
5-HT2C receptors with high affinity and the serotonin
5-HT2A receptor with moderate affinity.
[30]
[31] The result of the increased
serotonergic and
noradrenergic
neurotransmission is a feeling of fullness and reduced appetite.
The combination of fenfluramine with
phentermine , a
norepinephrine–dopamine releasing agent acting primarily on norepinephrine, results in a well-balanced
serotonin–norepinephrine releasing agent with weaker effects of dopamine release.
[27]
[28]
Fenfluramine, phentermine, and monoamine release (
EC50 Tooltip Half-maximal effective concentration , nM)
Drug
NE Tooltip Norepinephrine
DA Tooltip Dopamine
5-HT Tooltip Serotonin
Type
Ref
Fenfluramine
739
>10,000
79.3–108
SRA Tooltip Serotonin–norepinephrine releasing agent
[32]
[27]
[28]
D -Fenfluramine
302
>10,000
51.7
SNRA Tooltip Serotonin–norepinephrine releasing agent
[32]
[27]
L -Fenfluramine
>10,000
>10,000
147
SRA
[27]
[33]
Norfenfluramine
168–170
1,900–1,925
104
SNRA
[27]
[28]
Phentermine
39.4
262
3,511
NDRA Tooltip Norepinephrine–dopamine releasing agent
[32]
Fenfluramine was identified as a
potent
positive modulator of the
σ1 receptor in 2020 and this action may be involved in its therapeutic benefits in the treatment of seizures.
[13]
[14]
Pharmacokinetics
The
elimination half-life of fenfluramine has been reported as ranging from 13 to 30 hours.
[5] The mean elimination half-lives of its enantiomers have been found to be 19 hours for dexfenfluramine and 25 hours for levfenfluramine.
[8] Norfenfluramine, the major
active metabolite of fenfluramine, has an elimination half-life that is about 1.5 to 2 times as long as that of fenfluramine, with mean values of 34 hours for dexnorfenfluramine and 50 hours for levnorfenfluramine.
[8]
Chemistry
Fenfluramine is a
substituted amphetamine and is also known as 3-trifluoromethyl-N -ethylamphetamine.
[8] It is a
racemic mixture of two
enantiomers ,
dexfenfluramine and
levofenfluramine .
[8] Some
analogues of fenfluramine include
norfenfluramine ,
benfluorex ,
flucetorex , and
fludorex .
History
Fenfluramine was developed in the early 1960s and was introduced in
France in 1963.
[8] Approximately 50 million Europeans were treated with fenfluramine for appetite suppression between 1963 and 1996.
[8] Fenfluramine was approved in the
United States in 1973.
[8] The combination of fenfluramine and phentermine was proposed in 1984.
[8] Approximately 5 million people in the United States were given fenfluramine or dexfenfluramine with or without phentermine between 1996 and 1998.
[8]
In the early 1990s, French researchers reported an association of fenfluramine with primary
pulmonary hypertension and
dyspnea in a small sample of patients.
[8] Fenfluramine was withdrawn from the U.S. market in 1997 after reports of
heart valve disease
[34]
[16] and continued findings of pulmonary hypertension, including a condition known as
cardiac fibrosis .
[35] It was subsequently withdrawn from other markets around the world. It was banned in India in 1998.
[36]
Fenfluramine was an
appetite suppressant which was used to treat
obesity .
[8] It was used both on its own and,
in combination with phentermine , as part of the
anti-obesity medication Fen-Phen.
[8]
In June 2020, fenfluramine was approved for medical use in the United States with an indication to treat Dravet syndrome.
[7]
[37]
The effectiveness of fenfluramine for the treatment of seizures associated with Dravet syndrome was demonstrated in two clinical studies in 202 subjects between ages two and eighteen.
[7] The studies measured the change from baseline in the frequency of convulsive seizures.
[7] In both studies, subjects treated with fenfluramine had significantly greater reductions in the frequency of convulsive seizures during the trials than subjects who received placebo (inactive treatment).
[7] These reductions were seen within 3–4 weeks, and remained generally consistent over the 14- to 15-week treatment periods.
[7]
The U.S.
Food and Drug Administration (FDA) granted the application for fenfluramine
priority review and
orphan drug designations.
[7]
[38]
[39] The FDA granted approval of Fintepla to Zogenix, Inc.
[7]
On 15 October 2020, the
Committee for Medicinal Products for Human Use (CHMP) of the
European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Fintepla, intended for the treatment of seizures associated with Dravet syndrome.
[40] Fenfluramine was approved for medical use in the European Union in December 2020.
[3]
Society and culture
Legal status
Fenfluramine is a prescription medication in the US. Fenfluramine was removed from Schedule IV of the Controlled Substances Act in December 2022.
[41]
Recreational use
Unlike various other amphetamine derivatives, fenfluramine is reported to be
dysphoric , "unpleasantly
lethargic ", and non-
addictive at therapeutic doses.
[42] However, it has been reported to be used recreationally at high doses ranging between 80 and 400 mg, which have been described as producing
euphoria ,
amphetamine -like effects,
sedation , and
hallucinogenic effects, along with
anxiety ,
nausea ,
diarrhea , and sometimes
panic attacks , as well as
depressive
symptoms once the drug had worn off.
[42]
[43]
[44] At very high doses (e.g., 240 mg, or between 200 and 600 mg), fenfluramine induces a
psychedelic state resembling that produced by
lysergic acid diethylamide (LSD).
[44]
[45] Indirect (via induction of serotonin release) and/or direct activation of the 5-HT2A receptor would be expected to be responsible for the psychedelic effects of the drug at sufficient doses.
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Further reading
Gustafsson BI, Tømmerås K, Nordrum I, Loennechen JP, Brunsvik A, Solligård E, Fossmark R, Bakke I, Syversen U, Waldum H (March 2005).
"Long-term serotonin administration induces heart valve disease in rats" . Circulation . 111 (12): 1517–22.
doi :
10.1161/01.CIR.0000159356.42064.48 .
PMID
15781732 .
Welch JT, Lim DS (November 2007). "The synthesis and biological activity of pentafluorosulfanyl analogs of fluoxetine, fenfluramine, and norfenfluramine". Bioorganic & Medicinal Chemistry . 15 (21): 6659–6666.
doi :
10.1016/j.bmc.2007.08.012 .
PMID
17765553 .
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lurasidone ,
quetiapine ,
ziprasidone )
Azapirones (e.g.,
buspirone ,
eptapirone ,
gepirone ,
perospirone ,
tandospirone )
Bay R 1531
Befiradol
BMY-14802
Cannabidiol
Dimemebfe
Dopamine
Ebalzotan
Eltoprazine
Enciprazine
Ergolines (e.g.,
bromocriptine ,
cabergoline ,
dihydroergotamine ,
ergotamine ,
lisuride ,
LSD ,
methylergometrine (methylergonovine) ,
methysergide ,
pergolide )
F-11,461
F-12826
F-13714
F-14679
F-15063
F-15,599
Flesinoxan
Flibanserin
Flumexadol
Hypidone
Lesopitron
LY-293284
LY-301317
mCPP
MKC-242
Naluzotan
NBUMP
Osemozotan
Oxaflozane
Pardoprunox
Piclozotan
Rauwolscine
Repinotan
Roxindole
RU-24,969
S-14,506
S-14671
S-15535
Sarizotan
Serotonin (5-HT)
SSR-181507
Sunepitron
Tryptamines (e.g.,
5-CT ,
5-MeO-DMT ,
5-MT ,
bufotenin ,
DMT ,
indorenate ,
N-Me-5-HT ,
psilocin ,
psilocybin )
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
Dotarizine
Ergolines (e.g.,
metergoline )
FCE-24379
Flopropione
GR-46611
Isamoltane
Lecozotan
Mefway
Metitepine (methiothepin)
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