TABLE 8

Summary of in vivo pharmacological effects of TAAR1-selective agonists

Model/ParadigmMouseRatCynomolgus Monkey
Schizophrenia positive symptoms
 Cocaine-induced LMAacRO6017, RO3648, RO6390, RO3397RO3648
 L-687,414–induced LMAacRO6017, RO3648, RO6390, RO3397
 PCP-induced LMAcRO6390, RO3397
 DAT-KO (reduction of LMA)a,bRO6017, RO3648
 NR1-KD (reduction of LMA)a,bRO3648
Schizophrenia cognitive symptoms
 Object retrievalb,cRO3648, RO6390, RO3397
 Attentional set-shiftingcRO6390
Antidepression/stress-reducing
 Forced swim testbRO3648, RO3397
 Differential reinforcement of low-rate behaviorb,cRO3648, RO6390, RO3397
 Stress-induced hyperthermiaa,bRO6017, RO3648
Wake-promotingc,dRO3397RO3680, RO3397
Antiaddiction
 Cocaine self-administrationb,eRO3648, RO6390
 Cocaine-ICSSeRO6390, RO3397
 Context-induced cocaine relapsefRO3648, RO6390
 Cocaine reward memorygRO6017
 Abuse-related effects of cocainehRO3397
 Abuse-related effects of methamphetamineiRO3397
 Methamphetamine self-administrationjRO3648
 Methamphetamine-induced impulsivitykRO3397
 Nicotine self-administration, nicotine-induced sensitization, reinstatement of nicotine seekinglRO6017, RO3397
 Morphine-induced sensitization, morphine self-administrationmRO3397
 Compulsive binge-like eatingnRO6390
Antidiabetic
 oGTToRO6017
 oGTT in diabetic db/db mice, DIO mice, and diet-induced obese Glp1R-KO miceoRO6017
 Gastric emptyingoRO6017RO3397
 Reduction of weight gain and body weightc,oRO6017RO3397
 Reduction of weight gain induced by antipsychotic olanzapinecRO3397
No EPS liability (no effect on catalepsy)b,cRO3648, RO6390, RO3397
 Reduction of haloperidol-induced catalepsyb,cRO3648, RO6390, RO3397
  • DIO, diet-induced obese; EPS, extrapyramidal side-effects; ICSS, intracranial self-stimulation; LMA, locomotor activity; oGTT, oral glucose tolerance test; RO3397, RO5263397; RO3648, RO5203648; RO6017, RO5166017; RO6390, RO5256390;.

  • a Revel et al. (2011).

  • b Revel et al. (2012b).

  • c Revel et al. (2013).

  • d Schwartz et al. (2017).

  • e Pei et al. (2015).

  • f Pei et al. (2014).

  • g Liu et al. (2016).

  • h Thorn et al. (2014a).

  • i Jing and Li (2015).

  • j Cotter et al. (2015).

  • k Xue et al. (2018).

  • l Liu et al. (2018).

  • m Liu et al. (2017a).

  • n Ferragud et al. (2017).

  • o Raab et al. (2015).