TABLE 5

PDE4 inhibitors tested for their potential to induce emesis-like behavior (rodents) or emesis compared with rolipram

CompoundEmetic(-like) DoseEmetic(-like) Dose Ratio to RolipramAdministration RouteSpeciesTestStudy
µg/kg
Rolipram300IntraperitonealMouseXylazine/ketamine/anesthesia testVanmierlo et al., 2016
 Roflumilast300010
R-rolipram100SubcutaneousMouseXylazine/ketamine/anesthesia testRobichaud et al., 2002b
 S-rolipram100010
 PMNPQ10.01
 CT-2450>30,000>300
Rolipram100IntravenousMouseXylazine/ketamine/anesthesia testBurgin et al., 2010
 D157140100.1
 D158681>1000>10
 D1591531001
 D159382300.3
 D159404>3000>30
 D159687>3000>30
Rolipram30SubcutaneousMouseXylazine/ketamine/anesthesia testRicciarelli et al., 2017
 GEBR32a>3000>30
Rolipram30SubcutaneousMouseXylazine/ketamine/anesthesia testBruno et al., 2011
 GEBR7b30010
Rolipram500IntragastricMouseXylazine/ketamine/anesthesia testZhou et al., 2017
 10j>1500>3
Rolipram800OralDogEmesis incidenceZhou et al., 2017
 10j>800>1
Rolipram400OralRatPica feedingDavis et al., 2009
 Roflumilast1570>3.5
 Cilomilast6410>16
 EPPA-124,260>60
Rolipram500OralDogEmesis incidenceZhang et al., 2013
 Chlorbipram>1000>2
 Chlorbipram hydrochloride>1070>2
Rolipram<100OralDogEmesis incidenceNose et al., 2016
 Roflumilast500>5
 GPD-11161000>10
Rolipram3000OralFerretEmesis incidenceAoki et al., 2001b
 YM97630,00010
 RP7340130001
 CPP84030,00010
Rolipram10,000OralFerretEmesis incidenceGale et al., 2003
 V11294>30,000>3
Rolipram40IntraperitonealMouseAcute gastric retention measurementMcDonough et al., 2020a
 Piclamilast2005
 YM976100025