Analysis of information sources in references of the Wikipedia article "EPPTB" in English language version.
The TAAR1-selective antagonist EPPTB blocked methamphetamine- and bupropion-stimulated chloride conductance in Xenopous oocytes co-expressing mouse TAAR1 and the human cystic fibrosis transmembrane conductance regulator in a concentration-dependent manner with IC50's of 2.3±0.3nM and 4.3±0.7nM, respectively. [...] EPPTB displayed no affinity for mouse biogenic amine transporters nor did it produce a significant phenotype in wildtype or taar1-/- mice. In contrast, at the highest dose tested (100 mg/kg, i.p.) EPPTB inhibited approximately 70% of methamphetamine-stimulated (3 mg/kg, i.p.) activity in wildtype mice while having no effect on similarly treated [TAAR1] knockout mice. Intraperitoneal co-administration of methamphetamine (3 mg/kg) and bupropion (50 mg/kg) to wildtype mice produced greater activity than either drug alone, an effect absent from [TAAR1] knockout mice. [...] The existence of a methamphetamine-activated G protein-coupled receptor that is also activated by bupropion [...]
Hallucinogens: Lysergic acid diethylamide (LSD) has been reported as a TAAR1 agonist (Bunzow et al., 2001). Treatment with a TAAR1 antagonist EPPTB significantly blocked the inhibitory effect of LSD on dopaminergic neurons (De Gregorio et al., 2016). [...] Intriguingly, the TAAR1 agonist RO5166017 inhibited while the TAAR1 antagonist EPPTB promoted the firing rates of dopamine neurons in VTA and serotonin neurons in dorsal raphe nucleus (Revel et al., 2011). Moreover, dopamine neurons and serotonin neurons of TAAR1-KO mice showed increased firing rates (Revel et al., 2011).
EPPTB is a potent mTAAR1 antagonist (IC50 = 27.5 nM) but is 272-fold and 165-fold less potent at hTAAR1 (IC50 = 7.5 μM) and rTAAR1 (IC50 = 4.5 μM), respectively.14 Additional studies have shown that EPPTB may be an inverse agonist, as the compound was able to reduce mTAAR1-stimulated cAMP production (−12.3 ± 4.7%).14 Because of its favorable brain/plasma ratio of 0.5, EPPTB has been used in animal studies examining DA neurotransmission,14 but its high clearance limits the extent of studies that can be performed.1,15–16 Therefore, additional antagonists with better ADME properties and potency profiles are needed to help further explore TAAR1 pharmacology.1,16
TAAR1 agonists, such as p-tyramine or the synthetic agonist RO5166017, inhibit the firing frequency of VTA DA neurons and DRN 5-HT neurons, whereas the TAAR1 antagonist EPPTB dramatically increases their firing rates (11,12). [...] Interestingly, RO5203648 blocked hyperdopaminergic- and hypoglutamatergic-induced hyperlocomotion in vivo, similar to the "full" agonist RO5166017 (11), whereas it increased firing activity of DA and 5-HT neurons in vitro, similar to the antagonist EPPTB (11,12). This observation indicates that, in vitro, TAAR1 is constitutively active and/or tonically activated by endogenous agonist(s), a situation where partial agonism produces antagonistic-like effects on firing activity. [...] The only selective TAAR1 antagonist currently available is EPPTB (RO5212773) (Bradaia et al., 2009). Pharmacological characterization suggests that EPPTB is a TAAR1 antagonist/inverse agonist (Stalder et al., 2011). EPPTB could increase the firing rate of DA neurons in the brain slice of VTA from WT mice but not from TAAR1-KO mice. EPPTB also prevented TAAR1 agonist p-tyramine (p-try)-induced reduction of the firing rate of DA neurons (Bradaia et al., 2009). The information on the in vivo pharmacological activities of EPPTB is sparse. Therefore, more systematic studies of EPPTB in vivo and the development of new TAAR1 antagonists would greatly boost the TAAR1 research.
None of the drugs applied changed DA uptake because the Tau and half-life values were comparable among the naïve and treated brain slices (data not shown). [...] Importantly, we have documented that neither Tau nor the half-life of released DA are changed in slices from TAAR1-KO animals, indicating that TAAR1-KO mice exhibit unaltered DA uptake ability and thereby normal dopamine transporter (DAT) functionality. It is believed that Tau and the half-life of released DA are reliable measures for detecting changes in DA uptake because they are strongly correlated with changes in the Km of DAT mediated DA uptake (Yorgason et al., 2011). Thus, these neurochemical in vivo studies, as well as previous demonstrations of the functional activity of TAAR1 ligands in mice lacking the DAT (Sotnikova et al., 2004; Revel et al., 2012a), provide little support for the postulated role of TAAR1 in modulating DAT activity that is based mostly on in vitro cell culture experiments (Miller et al., 2005; Xie et al., 2008; Miller, 2011). [...] Importantly, we have documented that neither Tau nor the half-life of released DA are changed in slices from TAAR1-KO animals, indicating that TAAR1-KO mice exhibit unaltered DA uptake ability and thereby normal dopamine transporter (DAT) functionality. It is believed that Tau and the half-life of released DA are reliable measures for detecting changes in DA uptake because they are strongly correlated with changes in the Km of DAT mediated DA uptake (Yorgason et al., 2011). Thus, these neurochemical in vivo studies, as well as previous demonstrations of the functional activity of TAAR1 ligands in mice lacking the DAT (Sotnikova et al., 2004; Revel et al., 2012a), provide little support for the postulated role of TAAR1 in modulating DAT activity that is based mostly on in vitro cell culture experiments (Miller et al., 2005; Xie et al., 2008; Miller, 2011).
The endogenous TAAR1 agonist pTyr inhibits the firing frequency of DA neurons in the VTA, where Taar1 is expressed (10), whereas blockade of TAAR1 with EPPTB strongly increases their firing rate (17).
Similar to TYR, RO5166017 reduced the firing rate of VTA dopamine neurons and DRN serotonin neurons in brain slices from WT but not TAAR1-KO mice, through the activation of K+-mediated outward current, which can be blocked by TAAR1 antagonist EPPTB [38]. [...] Intriguingly, unlike TAAR1 full agonists, RO5203648 increased the firing frequency of VTA dopamine neurons and DRN serotonin neurons in vitro, similar to TAAR1 antagonist EPPTB [40]. [...] EPPTB—Currently, there is only one TAAR1 antagonist engineered for studying the role of TAAR1 in modulating the monoaminergic system. EPPTB was developed in 2009 by Bradaia and colleagues, and showed higher affinity to mouse TAAR1 than rat and human TAAR1 [81]. [...] EPPTB prevented the inhibition of firing frequency of dopamine neurons induced by non-selective TAAR1 agonist TYR in dopamine neurons of WT but not TAAR1-KO mice [81], suggesting a high selectivity. Given that TAAR1 has an inhibitory role in the dopaminergic system, which contributes to the alleviation of substance use disorder, the antagonism of TAAR1 may have minimal effects in drug addiction. However, it shows potential in preventing hypodopaminergic functions and thus may be useful for the treatment of disorders like Parkinson's disease [56].
Consistent with this, the firing rate of dopaminergic VTA neurons is increased in TAAR1-KO mice and enhanced by the TAAR1 antagonist EPPTB [72,84]. Interestingly, the partial agonists RO5203648 and RO5263397 also increase VTA DA neuron firing suggesting that, in vitro, TAAR1 is constitutively active and/or tonically activated by endogenous agonists, a situation where partial agonism produces a net antagonistic effect [74,111]. The extent to which such differential effects occur in vivo remains to be determined. [...] Similar to the findings in the VTA, full and partial agonists increase and decrease serotonergic neuronal firing in the DRN, respectively [74,86]. These effects were TAAR1- dependent as they were not observed in TAAR1-KO mice and reversed by the antagonist EPPTB [74,86].
{{cite book}}: |journal= ignored (help)[...] EPPTB's effect on the spontaneous locomotor activity in a familiar environment displayed by WT and taar1-deficient mice chronically exposed to 3 mg/kg METH (i.p.) over a range of doses was examined. The results of this study (Grandy, 2014; SfN abstracts) support the interpretation that EPPTB prevents to a significant degree METH-stimulated locomotor activity but only in WT mice with a history of chronic METH exposure.
On the other hand, HTS approaches [100] followed by structure-activity optimization allowed for the discovery of the hTAAR1 antagonist RTI-7470-44, endowed with a species-specificity preference over mTAAR1 (Figure 11A) [99]. RTI-7470-44 displayed good blood–brain barrier permeability, moderate metabolic stability, and a favorable preliminary off-target profile. In addition, RTI-7470-44 increased the spontaneous firing rate of mouse ventral tegmental area (VTA) dopaminergic neurons and blocked the effects of the known TAAR1 agonist RO5166017. [...] Figure 11. (A) Chemical structures of the available hTAAR1 agonists: EPPTB [98], RTI-7470-44 [99], and 4c [33], [...] RTI-7470-44: hTAAR1 IC50 = 0.0084 μM, mTAAR1 IC50 = 1.190 μM.
Studies have shown that there are considerable functional and pharmacological differences between hTA1 and TA1 in rats (rTA1) or mice (mTA1)12, with key implications for translating findings from preclinical models into human therapies. For instance, TYR has been reported to be ~30 times more potent at rTA1 than hTA1, and the antagonist EPPTB was shown to have an affinity of ~1 nM at mTA1 but does not appear to bind hTA132. Inversely, the recently reported TA1 antagonist RTI-7470-44 has an IC50 of about 8 nM at hTA1 but shows ~90-fold and ~140-fold reduced potencies at rTA1 and mTA1, respectively33.
Similar to EPPTB, RTI-7470-44 could increase the spontaneous firing rate of dopaminergic neurons in mice VTA slices and prevent the effects of TAAR1 agonist RO5166017 (Decker et [...] Furthermore, RTI-7470-44 has appropriate properties for in vivo use, including favorable preliminary off-target profile, moderate metabolic stability, and good blood-brain barrier permeability [...] However, currently there is no behavioral study that investigated the effects of RTI-7470-44. Compared to the limited literature on TAAR1 antagonists, many TAAR1 agonists have been [...]
The endogenous TAAR1 agonist pTyr inhibits the firing frequency of DA neurons in the VTA, where Taar1 is expressed (10), whereas blockade of TAAR1 with EPPTB strongly increases their firing rate (17).
Studies have shown that there are considerable functional and pharmacological differences between hTA1 and TA1 in rats (rTA1) or mice (mTA1)12, with key implications for translating findings from preclinical models into human therapies. For instance, TYR has been reported to be ~30 times more potent at rTA1 than hTA1, and the antagonist EPPTB was shown to have an affinity of ~1 nM at mTA1 but does not appear to bind hTA132. Inversely, the recently reported TA1 antagonist RTI-7470-44 has an IC50 of about 8 nM at hTA1 but shows ~90-fold and ~140-fold reduced potencies at rTA1 and mTA1, respectively33.
Hallucinogens: Lysergic acid diethylamide (LSD) has been reported as a TAAR1 agonist (Bunzow et al., 2001). Treatment with a TAAR1 antagonist EPPTB significantly blocked the inhibitory effect of LSD on dopaminergic neurons (De Gregorio et al., 2016). [...] Intriguingly, the TAAR1 agonist RO5166017 inhibited while the TAAR1 antagonist EPPTB promoted the firing rates of dopamine neurons in VTA and serotonin neurons in dorsal raphe nucleus (Revel et al., 2011). Moreover, dopamine neurons and serotonin neurons of TAAR1-KO mice showed increased firing rates (Revel et al., 2011).
EPPTB is a potent mTAAR1 antagonist (IC50 = 27.5 nM) but is 272-fold and 165-fold less potent at hTAAR1 (IC50 = 7.5 μM) and rTAAR1 (IC50 = 4.5 μM), respectively.14 Additional studies have shown that EPPTB may be an inverse agonist, as the compound was able to reduce mTAAR1-stimulated cAMP production (−12.3 ± 4.7%).14 Because of its favorable brain/plasma ratio of 0.5, EPPTB has been used in animal studies examining DA neurotransmission,14 but its high clearance limits the extent of studies that can be performed.1,15–16 Therefore, additional antagonists with better ADME properties and potency profiles are needed to help further explore TAAR1 pharmacology.1,16
TAAR1 agonists, such as p-tyramine or the synthetic agonist RO5166017, inhibit the firing frequency of VTA DA neurons and DRN 5-HT neurons, whereas the TAAR1 antagonist EPPTB dramatically increases their firing rates (11,12). [...] Interestingly, RO5203648 blocked hyperdopaminergic- and hypoglutamatergic-induced hyperlocomotion in vivo, similar to the "full" agonist RO5166017 (11), whereas it increased firing activity of DA and 5-HT neurons in vitro, similar to the antagonist EPPTB (11,12). This observation indicates that, in vitro, TAAR1 is constitutively active and/or tonically activated by endogenous agonist(s), a situation where partial agonism produces antagonistic-like effects on firing activity. [...] The only selective TAAR1 antagonist currently available is EPPTB (RO5212773) (Bradaia et al., 2009). Pharmacological characterization suggests that EPPTB is a TAAR1 antagonist/inverse agonist (Stalder et al., 2011). EPPTB could increase the firing rate of DA neurons in the brain slice of VTA from WT mice but not from TAAR1-KO mice. EPPTB also prevented TAAR1 agonist p-tyramine (p-try)-induced reduction of the firing rate of DA neurons (Bradaia et al., 2009). The information on the in vivo pharmacological activities of EPPTB is sparse. Therefore, more systematic studies of EPPTB in vivo and the development of new TAAR1 antagonists would greatly boost the TAAR1 research.
None of the drugs applied changed DA uptake because the Tau and half-life values were comparable among the naïve and treated brain slices (data not shown). [...] Importantly, we have documented that neither Tau nor the half-life of released DA are changed in slices from TAAR1-KO animals, indicating that TAAR1-KO mice exhibit unaltered DA uptake ability and thereby normal dopamine transporter (DAT) functionality. It is believed that Tau and the half-life of released DA are reliable measures for detecting changes in DA uptake because they are strongly correlated with changes in the Km of DAT mediated DA uptake (Yorgason et al., 2011). Thus, these neurochemical in vivo studies, as well as previous demonstrations of the functional activity of TAAR1 ligands in mice lacking the DAT (Sotnikova et al., 2004; Revel et al., 2012a), provide little support for the postulated role of TAAR1 in modulating DAT activity that is based mostly on in vitro cell culture experiments (Miller et al., 2005; Xie et al., 2008; Miller, 2011). [...] Importantly, we have documented that neither Tau nor the half-life of released DA are changed in slices from TAAR1-KO animals, indicating that TAAR1-KO mice exhibit unaltered DA uptake ability and thereby normal dopamine transporter (DAT) functionality. It is believed that Tau and the half-life of released DA are reliable measures for detecting changes in DA uptake because they are strongly correlated with changes in the Km of DAT mediated DA uptake (Yorgason et al., 2011). Thus, these neurochemical in vivo studies, as well as previous demonstrations of the functional activity of TAAR1 ligands in mice lacking the DAT (Sotnikova et al., 2004; Revel et al., 2012a), provide little support for the postulated role of TAAR1 in modulating DAT activity that is based mostly on in vitro cell culture experiments (Miller et al., 2005; Xie et al., 2008; Miller, 2011).
The endogenous TAAR1 agonist pTyr inhibits the firing frequency of DA neurons in the VTA, where Taar1 is expressed (10), whereas blockade of TAAR1 with EPPTB strongly increases their firing rate (17).
Similar to TYR, RO5166017 reduced the firing rate of VTA dopamine neurons and DRN serotonin neurons in brain slices from WT but not TAAR1-KO mice, through the activation of K+-mediated outward current, which can be blocked by TAAR1 antagonist EPPTB [38]. [...] Intriguingly, unlike TAAR1 full agonists, RO5203648 increased the firing frequency of VTA dopamine neurons and DRN serotonin neurons in vitro, similar to TAAR1 antagonist EPPTB [40]. [...] EPPTB—Currently, there is only one TAAR1 antagonist engineered for studying the role of TAAR1 in modulating the monoaminergic system. EPPTB was developed in 2009 by Bradaia and colleagues, and showed higher affinity to mouse TAAR1 than rat and human TAAR1 [81]. [...] EPPTB prevented the inhibition of firing frequency of dopamine neurons induced by non-selective TAAR1 agonist TYR in dopamine neurons of WT but not TAAR1-KO mice [81], suggesting a high selectivity. Given that TAAR1 has an inhibitory role in the dopaminergic system, which contributes to the alleviation of substance use disorder, the antagonism of TAAR1 may have minimal effects in drug addiction. However, it shows potential in preventing hypodopaminergic functions and thus may be useful for the treatment of disorders like Parkinson's disease [56].
Consistent with this, the firing rate of dopaminergic VTA neurons is increased in TAAR1-KO mice and enhanced by the TAAR1 antagonist EPPTB [72,84]. Interestingly, the partial agonists RO5203648 and RO5263397 also increase VTA DA neuron firing suggesting that, in vitro, TAAR1 is constitutively active and/or tonically activated by endogenous agonists, a situation where partial agonism produces a net antagonistic effect [74,111]. The extent to which such differential effects occur in vivo remains to be determined. [...] Similar to the findings in the VTA, full and partial agonists increase and decrease serotonergic neuronal firing in the DRN, respectively [74,86]. These effects were TAAR1- dependent as they were not observed in TAAR1-KO mice and reversed by the antagonist EPPTB [74,86].
{{cite book}}: |journal= ignored (help)[...] EPPTB's effect on the spontaneous locomotor activity in a familiar environment displayed by WT and taar1-deficient mice chronically exposed to 3 mg/kg METH (i.p.) over a range of doses was examined. The results of this study (Grandy, 2014; SfN abstracts) support the interpretation that EPPTB prevents to a significant degree METH-stimulated locomotor activity but only in WT mice with a history of chronic METH exposure.
On the other hand, HTS approaches [100] followed by structure-activity optimization allowed for the discovery of the hTAAR1 antagonist RTI-7470-44, endowed with a species-specificity preference over mTAAR1 (Figure 11A) [99]. RTI-7470-44 displayed good blood–brain barrier permeability, moderate metabolic stability, and a favorable preliminary off-target profile. In addition, RTI-7470-44 increased the spontaneous firing rate of mouse ventral tegmental area (VTA) dopaminergic neurons and blocked the effects of the known TAAR1 agonist RO5166017. [...] Figure 11. (A) Chemical structures of the available hTAAR1 agonists: EPPTB [98], RTI-7470-44 [99], and 4c [33], [...] RTI-7470-44: hTAAR1 IC50 = 0.0084 μM, mTAAR1 IC50 = 1.190 μM.
Studies have shown that there are considerable functional and pharmacological differences between hTA1 and TA1 in rats (rTA1) or mice (mTA1)12, with key implications for translating findings from preclinical models into human therapies. For instance, TYR has been reported to be ~30 times more potent at rTA1 than hTA1, and the antagonist EPPTB was shown to have an affinity of ~1 nM at mTA1 but does not appear to bind hTA132. Inversely, the recently reported TA1 antagonist RTI-7470-44 has an IC50 of about 8 nM at hTA1 but shows ~90-fold and ~140-fold reduced potencies at rTA1 and mTA1, respectively33.
Similar to EPPTB, RTI-7470-44 could increase the spontaneous firing rate of dopaminergic neurons in mice VTA slices and prevent the effects of TAAR1 agonist RO5166017 (Decker et [...] Furthermore, RTI-7470-44 has appropriate properties for in vivo use, including favorable preliminary off-target profile, moderate metabolic stability, and good blood-brain barrier permeability [...] However, currently there is no behavioral study that investigated the effects of RTI-7470-44. Compared to the limited literature on TAAR1 antagonists, many TAAR1 agonists have been [...]
Hallucinogens: Lysergic acid diethylamide (LSD) has been reported as a TAAR1 agonist (Bunzow et al., 2001). Treatment with a TAAR1 antagonist EPPTB significantly blocked the inhibitory effect of LSD on dopaminergic neurons (De Gregorio et al., 2016). [...] Intriguingly, the TAAR1 agonist RO5166017 inhibited while the TAAR1 antagonist EPPTB promoted the firing rates of dopamine neurons in VTA and serotonin neurons in dorsal raphe nucleus (Revel et al., 2011). Moreover, dopamine neurons and serotonin neurons of TAAR1-KO mice showed increased firing rates (Revel et al., 2011).
EPPTB is a potent mTAAR1 antagonist (IC50 = 27.5 nM) but is 272-fold and 165-fold less potent at hTAAR1 (IC50 = 7.5 μM) and rTAAR1 (IC50 = 4.5 μM), respectively.14 Additional studies have shown that EPPTB may be an inverse agonist, as the compound was able to reduce mTAAR1-stimulated cAMP production (−12.3 ± 4.7%).14 Because of its favorable brain/plasma ratio of 0.5, EPPTB has been used in animal studies examining DA neurotransmission,14 but its high clearance limits the extent of studies that can be performed.1,15–16 Therefore, additional antagonists with better ADME properties and potency profiles are needed to help further explore TAAR1 pharmacology.1,16
The endogenous TAAR1 agonist pTyr inhibits the firing frequency of DA neurons in the VTA, where Taar1 is expressed (10), whereas blockade of TAAR1 with EPPTB strongly increases their firing rate (17).
Similar to TYR, RO5166017 reduced the firing rate of VTA dopamine neurons and DRN serotonin neurons in brain slices from WT but not TAAR1-KO mice, through the activation of K+-mediated outward current, which can be blocked by TAAR1 antagonist EPPTB [38]. [...] Intriguingly, unlike TAAR1 full agonists, RO5203648 increased the firing frequency of VTA dopamine neurons and DRN serotonin neurons in vitro, similar to TAAR1 antagonist EPPTB [40]. [...] EPPTB—Currently, there is only one TAAR1 antagonist engineered for studying the role of TAAR1 in modulating the monoaminergic system. EPPTB was developed in 2009 by Bradaia and colleagues, and showed higher affinity to mouse TAAR1 than rat and human TAAR1 [81]. [...] EPPTB prevented the inhibition of firing frequency of dopamine neurons induced by non-selective TAAR1 agonist TYR in dopamine neurons of WT but not TAAR1-KO mice [81], suggesting a high selectivity. Given that TAAR1 has an inhibitory role in the dopaminergic system, which contributes to the alleviation of substance use disorder, the antagonism of TAAR1 may have minimal effects in drug addiction. However, it shows potential in preventing hypodopaminergic functions and thus may be useful for the treatment of disorders like Parkinson's disease [56].
Consistent with this, the firing rate of dopaminergic VTA neurons is increased in TAAR1-KO mice and enhanced by the TAAR1 antagonist EPPTB [72,84]. Interestingly, the partial agonists RO5203648 and RO5263397 also increase VTA DA neuron firing suggesting that, in vitro, TAAR1 is constitutively active and/or tonically activated by endogenous agonists, a situation where partial agonism produces a net antagonistic effect [74,111]. The extent to which such differential effects occur in vivo remains to be determined. [...] Similar to the findings in the VTA, full and partial agonists increase and decrease serotonergic neuronal firing in the DRN, respectively [74,86]. These effects were TAAR1- dependent as they were not observed in TAAR1-KO mice and reversed by the antagonist EPPTB [74,86].
[...] EPPTB's effect on the spontaneous locomotor activity in a familiar environment displayed by WT and taar1-deficient mice chronically exposed to 3 mg/kg METH (i.p.) over a range of doses was examined. The results of this study (Grandy, 2014; SfN abstracts) support the interpretation that EPPTB prevents to a significant degree METH-stimulated locomotor activity but only in WT mice with a history of chronic METH exposure.
On the other hand, HTS approaches [100] followed by structure-activity optimization allowed for the discovery of the hTAAR1 antagonist RTI-7470-44, endowed with a species-specificity preference over mTAAR1 (Figure 11A) [99]. RTI-7470-44 displayed good blood–brain barrier permeability, moderate metabolic stability, and a favorable preliminary off-target profile. In addition, RTI-7470-44 increased the spontaneous firing rate of mouse ventral tegmental area (VTA) dopaminergic neurons and blocked the effects of the known TAAR1 agonist RO5166017. [...] Figure 11. (A) Chemical structures of the available hTAAR1 agonists: EPPTB [98], RTI-7470-44 [99], and 4c [33], [...] RTI-7470-44: hTAAR1 IC50 = 0.0084 μM, mTAAR1 IC50 = 1.190 μM.
Studies have shown that there are considerable functional and pharmacological differences between hTA1 and TA1 in rats (rTA1) or mice (mTA1)12, with key implications for translating findings from preclinical models into human therapies. For instance, TYR has been reported to be ~30 times more potent at rTA1 than hTA1, and the antagonist EPPTB was shown to have an affinity of ~1 nM at mTA1 but does not appear to bind hTA132. Inversely, the recently reported TA1 antagonist RTI-7470-44 has an IC50 of about 8 nM at hTA1 but shows ~90-fold and ~140-fold reduced potencies at rTA1 and mTA1, respectively33.
Similar to EPPTB, RTI-7470-44 could increase the spontaneous firing rate of dopaminergic neurons in mice VTA slices and prevent the effects of TAAR1 agonist RO5166017 (Decker et [...] Furthermore, RTI-7470-44 has appropriate properties for in vivo use, including favorable preliminary off-target profile, moderate metabolic stability, and good blood-brain barrier permeability [...] However, currently there is no behavioral study that investigated the effects of RTI-7470-44. Compared to the limited literature on TAAR1 antagonists, many TAAR1 agonists have been [...]