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. Author manuscript; available in PMC: 2021 Mar 1.
Published in final edited form as: Exp Neurol. 2019 Dec 19;325:113145. doi: 10.1016/j.expneurol.2019.113145

Table 1.

Review of literature supporting anticonvulsant effect of 5-HT enhancing drugs in electrical, chemical, and genetic animal models of epilepsy.

MODEL SPECIES DRUG DOSE (mg/kg) STUDY PROTOCOL SEIZURE OUTCOME MEASURE REFERENCE
PTZ Zebrafish CIT, REB, BUP 10–300 μM 1 min before sz induction Seizure threshold Vermoesen et al. (2011)
PTZ Mouse REB, BUP 5–10; 10–40 30 min before sz induction Seizure threshold Vermoesen et al. (2011)
PTZ Mouse FLX 20 60 min before sz induction Survival Kecskemeti et al. (2005)
PTZ Mouse FLX 1–20 30 min before sz induction Seizure threshold, latency Ugale et al. (2004)
PTZ Mouse FLX 10, 15 30 min before sz induction Seizure threshold, susceptibility Borowicz et al. (2012)
PTZ Mouse HBK-14 20 30 min before sz induction Seizure threshold Pytka et al. (2017)
PTZ Mouse SRT 10 Drug for 14 days before sz induction Seizure threshold Heydari and Davoudi (2017)
PTZ Rat TNP 20–80 30 min before sz induction Seizure latency, frequency, severity Reeta et al. (2016)
PTZ Mouse SR 57227 1–10 30 min before sz induction Seizure latency, severity, mortality Li et al. (2014)
PTZ Mouse TNP 2.5–80 30 min before sz induction Seizure onset Uzbay et al. (2007)
PTZ Rat VEN 25–50 30 min before sz induction Seizure severity and latency Santos et al. (2002)
PTZ Mouse mCPBG, CIT 1–10; 0.1–50 30 min before sz induction Seizure threshold Payandemehr et al. (2012)
PTZ Mouse APZ 0.5–8 30, 60, 120 min before sz induction Seizure latency Shafaroodi et al. (2015)
PTZ/DBA/2 Mouse 5-HT 800 μg Intracranial injection 10 min before sz induction Seizure severity Schlesinger et al. (1969)
PTZ Mouse REB 4–15 30 min before sz induction Seizure threshold Poplawska et al. (2015)
PTZ (kindling) Mouse FLV 5–20 30 min before sz induction Seizure severity, brain dmg Alhaj et al. (2015)
Pilocarpine Zebrafish CIT 10–300 μM 1 min before sz induction Seizure threshold Vermoesen et al. (2011)
Pilocarpine Rat FLX 20 Drug for 5 days after sz induction Seizure frequency Hernandez et al. (2002)
Pilocarpine Rat FLX 20 Drug for 10 days once epileptic Seizure threshold Mazarati et al. (2008)
Pilocarpine Rat PAR 5 Drug for 4 days after sz induction Seizure frequency, severity, brain dmg Lin et al. (2017)
KA Mouse CIT 10 Drug for 7 days before sz induction Seizure severity Jaako et al. (2011)
KA Rat BUP 10, 50 30 min before sz induction Seizure latency, severity, brain dmg Lin et al. (2013)
KA Rat CIT, REB 15, 20–30 Drug for 4 days once epileptic Seizure frequency, duration Vermoesen et al. (2012)
MES Mouse APZ 1–2 60 min before sz induction Seizure mortality, tonic phase duration Shafaroodi et al. (2015)
MES Mouse BUP 15–30 30 min before sz induction Seizure threshold Tutka et al. (2004)
MES Mouse REB, FLX, CIT, DLX 0.1–30; 10; 20; 10 30 min before sz induction Seizure mortality Kruse et al. (2019)
MES Mouse VEN 12.5, 25 30 min before sz induction Seizure threshold Borowicz et al. (2011)
MES Mouse VEN 12.5, 25 Drug for 14 days before sz induction Seizure threshold Borowicz et al. (2011)
MES Mouse FLX 2.5, 5, 10 30 min before sz induction AED ED50 Leander (1992)
MES Rat FLX, FEN 10, 15 60 min before sz induction Hind limb extension Buterbaugh (1978)
MES Mouse DOI, CIT, TCB-2, MK-212 0.3, 1; 20; 10; 10 30 min before sz induction Seizure mortality Buchanan et al. (2014)
MES Mouse HBK-14, HBK-15 20 30 min before sz induction Seizure threshold Pytka et al. (2017)
MES Mouse FLX 10 60 min before sz induction Seizure threshold Raju et al. (1999)
MES/PTZ Mouse/Rat 5-HTP 100 30 min before sz induction Seizure threshold Killian and Frey (1973)
MES Mouse REB 8–16 30 min before sz induction Seizure threshold Borowicz et al. (2014)
6 Hz Corneal Stimulation Mouse HBK-14, HBK-15 20 30 min before sz induction Seizure threshold Pytka et al. (2017)
Ear shock Mouse FLX 15–25 30 min before sz induction Seizure threshold Borowicz et al. (2006)
Hippocampal kindling Rat FLX 10 nmol 15 min before sz induction Electrical threshold Wada et al. (1993)
Hippocampal kindling Rat 5-HTP 50 60 min before sz induction Electrical threshold Cavalheiro et al. (1981)
Hippocampal kindling Rat FLX 10 Drug for 21 days before sz induction Electrical threshold Wada et al. (1995)
Amygdala kindling Cat FLX 2–10 1–49 hr before seizure induction Electrical threshold Siegal and Murphy (1979)
Amygdala kindling Mouse FLX 10 Osmotic mini pump, 30 day administration Afterdischarge threshold Li et al. (2018)
GEPR-3 and GEPR-9 Rat FLX 30 1–5 hr before seizure induction Seizure severity Dailey et al. (1992)
GEPR-3 and GEPR-9 Rat FLX 7–20 Sz induced every 7 days for 28 days Seizure threshold Dailey et al. (1992)
GEPR-9 Rat FLX 15 60 min before sz induction Severity and latency Yan et al. (1994)
El mice Mouse CIT 0.01, 0.02, 0.04 Drug for 14 days before sz induction Seizure threshold Kabuto et al. (1994)
El mice Mouse FLX 10 Drug for 3 or 7 days before sz induction Seizure threshold Richman and Heinrichs (2007)
DBA/1 and PTZ Mouse 5-HTP 100–150 Drug for 2 days before sz induction S-IRA, seizure incidence Zhang et al. (2015)
DBA/1 Mouse FLX 30 30 min before sz induction S-IRA Zeng et al. (2015)
DBA/1 Mouse SRT 40–75 30 min before sz induction S-IRA, seizure incidence Faingold and Randall (2013)
DBA/1 Mouse FEN 10–40 30 min, 12 hr, 24 hr, or 72 hr before sz induction Seizure severity, ED50, S-IRA Tupal and Faingold (2019)
DBA/2 Mouse FLX 15–25 30 min or 72 hr before sz induction S-IRA, seizure incidence Tupal and Faingold (2006)
DBA/1 Mouse SR 57227, FLX 20–40; 40 30 min before sz induction S-IRA, seizure incidence Faingold et al. (2016)
DBA/1 Mouse FLX 15–70 acute, 20 chronic 30 min before or for 5 days before sz induction S-IRA, seizure incidence Faingold et al. (2011)
DBA/1 Mouse FLV, PAR,VEN 50–80; 75–100; 25–100 30, 60, 120 min prior to sz induction S-IRA, seizure incidence Faingold et al. (2014)
Audiogenic Sz Rat FLX 25 60 min before sz induction Seizure severity Ismaylova and Madzhidi (2012)
Audiogenic Sz Rat FLX 20 Drug for 14 days before sz induction Seizure severity Sarkissova et al. (2016)
WAG/Rij Absence Sz Rat FLX, DLX 30; 10–30 Drug administration for 7 weeks Seizure and immobility duration Citraro et al. (2015)
Flurothyl Mouse REB 20 Drug for 21 days before sz induction Seizure latency Ahern et al. (2006)
Focal pilocarpine Rat CIT 1 μM 4 hr intracranial infusion before sz induction Seizure severity Clinckers et al. (2004)
Focal bicuculline Rat FLX 5–20 60 min before sz induction Seizure frequency, severity Prendiville and Gale (1993)
Focal bicuculline Rat FLX 1.75–7 nM 15 min before sz induction Seizure threshold Pasini et al. (1992)
Picrotoxin Mouse FLX 20 65 min before sz induction Seizure latency Pericic et al. (2005)
Picrotoxin Mouse FLX 20 Drug for 5 days before sz induction Seizure latency Pericic et al. (2005)
4-AP Rat FLX 10 Drug for 7 days before sz induction Seizure latency, brain dmg Shiha et al. (2017)
4-AP Rat SRT 2.5, 25 4 hr before sz induction Seizure frequency, EEG changes Sitges et al. (2012)
4-AP Rat SRT 0.75 Drug for 7 days before sz induction Seizure frequency, EEG changes Sitges et al. (2012)
4-AP Rat SRT 0.75, 2.5 4 hr before sz induction Seizure suppression Sitges et al. (2016)

BUP, bupropion; CIT, citalopram; FEN, fenfluramine; FLV, fluvoxamine; FLX, fluoxetine; GEPR, genetically epilepsy prone rats; hr, hour; KA, kainic acid; MAP, maprotiline; min, minute; PAR, paroxetine; REB, reboxetine; SRT, sertraline; sz, seizure; VEN, venlafaxine; CLM, clemizole.