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Ayahuasca
Published in Mahendra Rai, Shandesh Bhattarai, Chistiane M. Feitosa, Wild Plants, 2020
Raquel Consul, Flávia Lucas, Maria Graça Campos
TAAR-1 belongs to a recently discovered class of receptors which can mediate the effects of DMT. As most research has focused on the action of DMT in the 5-HT receptor2A, there is little information on the role of TAAR-1 in the triggered effects. It is only known that there is a high affinity for the binding of DMT to this receptor and that it activates adenyl cyclase, leading to the accumulation of AMPc (Carbonaro and Gatch 2016, Barker 2018, Cameron and Olson 2018).
Stimulants and psychedelics
Published in Ilana B. Crome, Richard Williams, Roger Bloor, Xenofon Sgouros, Substance Misuse and Young People, 2019
All amphetamines have been identified as potent full agonists of trace amine-associated receptor 1 (TAAR-1) (Miller, 2011), which is important in the regulation of brain monoamines. Notably, amphetamines bind to TAAR-1 but not monoamine auto-receptors (e.g., D2 short, presynaptic α2, and presynaptic 5-HT1A) (ibid.; Grandy et al., 2016). Amphetamines exert their action primarily in the reward and executive function pathways of the brain; their administration results in the release of newly synthesised norepinephrine and dopamine (Bidwell et al., 2011; Miller, 2011), due to inhibition of the monoamine transporter function. This is in contrast to other types of stimulants, such as methylphenidate and cocaine, which act through storage pools of catecholamines (Borowsky et al., 2001; Eiden and Weihe, 2011; Miller, 2011). In addition, high doses of amphetamines release 5-hydroxytryptamine and may affect serotonergic neurons (Miller, 2011).
Novel multi-target ligands of dopamine and serotonin receptors for the treatment of schizophrenia based on indazole and piperazine scaffolds–synthesis, biological activity, and structural evaluation
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2023
Piotr Stępnicki, Olga Wronikowska-Denysiuk, Agata Zięba, Katarzyna M. Targowska-Duda, Agata Bartyzel, Martyna Z. Wróbel, Tomasz M. Wróbel, Klaudia Szałaj, Andrzej Chodkowski, Karolina Mirecka, Barbara Budzyńska, Emilia Fornal, Jadwiga Turło, Marián Castro, Agnieszka A. Kaczor
Certain environmental and genetic factors may predispose to development of schizophrenia; however, its exact causes remain unclear. There are several hypotheses aimed at explaining the underlying causes of the disease. The dominant one is based on the disturbances of dopaminergic neurotransmission in the mesolimbic circuit in the central nervous system, which leads to positive symptoms, such as hallucinations and delusions, and in the mesocortical circuit, which is suggested to produce negative symptoms, such as asociality or anhedonia5. Attempts are being made to develop antipsychotic drugs acting through a non-dopaminergic mechanism. In particular, the trace amine-associated receptor 1 (TAAR1) has come under the spotlight in recent years as a potential target for new drugs against schizophrenia6. TAAR1 belongs to the family of G-protein-coupled receptors (GPCRs) and is involved in modulation of dopaminergic, serotonergic, and glutamatergic neurotransmissions7. Two TAAR1 agonists, ulotaront and ralmitaront, currently undergo clinical trials6,8. In particular, the first one shows effectiveness in relation to positive, negative, and cognitive symptoms, and does not cause side effects characteristic of marketed antipsychotics, resulting mainly from the interaction with dopamine D2 receptor8.
Update on novel antipsychotics and pharmacological strategies for treatment-resistant schizophrenia
Published in Expert Opinion on Pharmacotherapy, 2022
Andrea de Bartolomeis, Mariateresa Ciccarelli, Licia Vellucci, Michele Fornaro, Felice Iasevoli, Annarita Barone
Trace amine-associated receptor 1 (TAAR1) is a G-protein-coupled receptor identified in several tissues including the olfactory epithelium and the central nervous system [139]. TAAR1 is activated by endogenous trace amines (Figure 1), which are structurally related to monoamines, such as serotonin and dopamine [140]. Trace amines are considered potential neuromodulators, since β-phenylethylamine and p-tyramine have been shown to modify the release and/or response to dopamine, norepinephrine, acetylcholine, and GABA [141]. TAAR1 interaction with D2R reduces the recruitment of β-arrestin 2, thereby silencing the GSK3β cascade via Akt [151]. Of interest, this intracellular pathway converges on the downstream targets activated by mood stabilizers, such as lithium. This peculiar feature of TAAR1 agonists could provide a novel therapeutic strategy for schizophrenia compared to current pharmacological standards [139].
What value do norepinephrine/dopamine dual reuptake inhibitors have to the current treatment of adult attention deficit hyperactivity disorder (ADHD) treatment armamentarium?
Published in Expert Opinion on Pharmacotherapy, 2022
Giulio Perugi, Ugo De Rosa, Margherita Barbuti
Amphetamines primarily act by inhibiting the reuptake of dopamine and norepinephrine through inhibition of DAT and NET. They also increase dopaminergic and noradrenergic transmission through inhibition of the vesicular monoamine transporter (VMAT-2), inhibition of catechol-methyltransferase (COMT), reduction in cytosolic monoamine oxidase (MAO) catabolism, and stimulation of the trace amine-associated receptor 1 (TAAR1) [11,16,17]. In addition, amphetamine-induced NET blockade in the prefrontal cortex, resulting in increased noradrenaline levels and alpha-1 receptor activation, appears to change the firing pattern of dopaminergic neurons in the ventral tegmental area that project to the nucleus accumbens [18]. Finally, amphetamines also appear to affect the glutamatergic, opioid and cholinergic systems [11].