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| Formula | C13H18N2O |
| Molar mass | 218.300 g·mol−1 |
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RO5256390 or RO-5256390 is a drug developed by Hoffmann-La Roche which acts as an agonist for the trace amine associated receptor 1, which has been shown to block compulsive and binge-like eating behavior in rats. For this reason, it is being investigated as a potential drug to treat binge eating disorder. [1] [2]
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A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, or target cell, may be another neuron, but could also be a gland or muscle cell.
Tryptamine is an indolamine metabolite of the essential amino acid, tryptophan. The chemical structure is defined by an indole—a fused benzene and pyrrole ring, and a 2-aminoethyl group at the second carbon (third aromatic atom, with the first one being the heterocyclic nitrogen). The structure of tryptamine is a shared feature of certain aminergic neuromodulators including melatonin, serotonin, bufotenin and psychedelic derivatives such as dimethyltryptamine (DMT), psilocybin, psilocin and others. Tryptamine has been shown to activate trace amine-associated receptors expressed in the mammalian brain, and regulates the activity of dopaminergic, serotonergic and glutamatergic systems. In the human gut, symbiotic bacteria convert dietary tryptophan to tryptamine, which activates 5-HT4 receptors and regulates gastrointestinal motility. Multiple tryptamine-derived drugs have been developed to treat migraines, while trace amine-associated receptors are being explored as a potential treatment target for neuropsychiatric disorders.
Sympathomimetic drugs are stimulant compounds which mimic the effects of endogenous agonists of the sympathetic nervous system. Examples of sympathomimetic effects include increases in heart rate, force of cardiac contraction, and blood pressure. The primary endogenous agonists of the sympathetic nervous system are the catecholamines, which function as both neurotransmitters and hormones. Sympathomimetic drugs are used to treat cardiac arrest and low blood pressure, or even delay premature labor, among other things.
Isoprenaline, or isoproterenol, is a medication used for the treatment of bradycardia, heart block, and rarely for asthma. It is a non-selective β adrenoceptor agonist that is the isopropylamine analog of epinephrine (adrenaline).
Quinpirole is a psychoactive drug and research chemical which acts as a selective D2 and D3 receptor agonist. It is used in scientific research. Quinpirole has been shown to increase locomotion and sniffing behavior in mice treated with it. At least one study has found that quinpirole induces compulsive behavior symptomatic of obsessive compulsive disorder in rats. Another study in rats show that quinpirole produces significant THC-like effects when metabolic degradation of anandamide is inhibited, supporting the hypothesis that these effects of quinpirole are mediated by cannabinoid CB1 receptors. Quinpirole may also reduce relapse in adolescent rat models of cocaine addiction.
A dopamine agonist(DA) is a compound that activates dopamine receptors. There are two families of dopamine receptors, D1-like and D2-like. They are all G protein-coupled receptors. D1- and D5-receptors belong to the D1-like family and the D2-like family includes D2, D3 and D4 receptors. Dopamine agonists are primarily used in the treatment of Parkinson's disease, and to a lesser extent, in hyperprolactinemia and restless legs syndrome. They are also used off-label in the treatment of clinical depression. The use of dopamine agonists is associated with impulse control disorders and dopamine agonist withdrawal syndrome (DAWS).
Trace amines are an endogenous group of trace amine-associated receptor 1 (TAAR1) agonists – and hence, monoaminergic neuromodulators – that are structurally and metabolically related to classical monoamine neurotransmitters. Compared to the classical monoamines, they are present in trace concentrations. They are distributed heterogeneously throughout the mammalian brain and peripheral nervous tissues and exhibit high rates of metabolism. Although they can be synthesized within parent monoamine neurotransmitter systems, there is evidence that suggests that some of them may comprise their own independent neurotransmitter systems.
Trace amine-associated receptors (TAARs), sometimes referred to as trace amine receptors, are a class of G protein-coupled receptors that were discovered in 2001. TAAR1, the first of six functional human TAARs, has gained considerable interest in academic and proprietary pharmaceutical research due to its role as the endogenous receptor for the trace amines phenethylamine, tyramine, and tryptamine – metabolic derivatives of the amino acids phenylalanine, tyrosine and tryptophan, respectively – ephedrine, as well as the synthetic psychostimulants, amphetamine, methamphetamine and methylenedioxymethamphetamine. In 2004, it was shown that mammalian TAAR1 is also a receptor for thyronamines, decarboxylated and deiodinated relatives of thyroid hormones. TAAR2–TAAR9 function as olfactory receptors for volatile amine odorants in vertebrates.
2C-H (2,5-dimethoxyphenethylamine) is a lesser-known substituted phenethylamine of the 2C family.
Norfenfluramine, or 3-trifluoromethylamphetamine, is a never-marketed drug of the amphetamine family that behaves as a serotonin and norepinephrine releasing agent and potent 5-HT2A, 5-HT2B, and 5-HT2C agonist. The action of norfenfluramine on 5-HT2B receptors on heart valves leads to a characteristic pattern of heart failure following proliferation of cardiac fibroblasts on the tricuspid valve, known as cardiac fibrosis. This side effect led to the withdrawal of fenfluramine as an anorectic agent worldwide, and to the withdrawal of benfluorex in Europe, as both fenfluramine and benfluorex form norfenfluramine as an active metabolite. It is a human TAAR1 agonist.
Animal psychopathology is the study of mental or behavioral disorders in non-human animals.
Trace amine associated receptor 6, also known as TAAR6, is a protein which in humans is encoded by the TAAR6 gene.
Trace amine-associated receptor 5 is a protein that in humans is encoded by the TAAR5 gene. In vertebrates, TAAR5 is expressed in the olfactory epithelium.
Trace amine-associated receptor 1 (TAAR1) is a trace amine-associated receptor (TAAR) protein that in humans is encoded by the TAAR1 gene. TAAR1 is an intracellular amine-activated Gs-coupled and Gq-coupled G protein-coupled receptor (GPCR) that is primarily expressed in several peripheral organs and cells, astrocytes, and in the intracellular milieu within the presynaptic plasma membrane of monoamine neurons in the central nervous system (CNS). TAAR1 was discovered in 2001 by two independent groups of investigators, Borowski et al. and Bunzow et al. TAAR1 is one of six functional human trace amine-associated receptors, which are so named for their ability to bind endogenous amines that occur in tissues at trace concentrations. TAAR1 plays a significant role in regulating neurotransmission in dopamine, norepinephrine, and serotonin neurons in the CNS; it also affects immune system and neuroimmune system function through different mechanisms.
Trace amine-associated receptor 9 is a protein that in humans is encoded by the TAAR9 gene.
Xylamidine is a drug which acts as an antagonist at the 5HT2A receptor, and to a lesser extent at the 5HT1A receptor. It does not cross the blood–brain barrier, which makes it useful for blocking peripheral serotonergic responses like cardiovascular and gastrointestinal effects, without producing the central effects of 5HT2A blockade such as sedation, or interfering with the central actions of 5HT2A agonists.
Phenylethanolamine, or β-hydroxyphenethylamine, is a trace amine with a structure similar to those of other trace phenethylamines as well as the catecholamine neurotransmitters dopamine, norepinephrine, and epinephrine. As an organic compound, phenylethanolamine is a β-hydroxylated phenethylamine that is also structurally related to a number of synthetic drugs in the substituted phenethylamine class. In common with these compounds, phenylethanolamine has strong cardiovascular activity and, under the name Apophedrin, has been used as a drug to produce topical vasoconstriction.
RO-5166017 is a drug developed by Hoffmann-La Roche which acts as a potent and selective agonist for the trace amine-associated receptor 1, with no significant activity at other targets. This is important for the study of the TAAR1 receptor, as while numerous other compounds are known which act as TAAR1 agonists, such as methamphetamine, MDMA and 3-iodothyronamine, all previously known TAAR1 agonists are either weak and rapidly metabolized, or have strong pharmacological activity at other targets, making it very difficult to assess which effects are due to TAAR1 activation. The discovery of RO-5166017 allows purely TAAR1 mediated effects to be studied, and in animal studies it was shown to prevent stress-induced hyperthermia and block dopamine-dependent hyperlocomotion, as well as blocking the hyperactivity which would normally be induced by an NMDA antagonist. The experiment was done in dopamine transporter knockout mice, and since TAAR1 affects the dopamine transporter, the results could be very different in humans.
EPPTB (RO-5212773) is a drug developed by Hoffmann-La Roche which acts as a potent and selective inverse agonist of trace amine-associated receptor 1 (TAAR1), with no significant activity at other targets. EPPTB is one of the first selective antagonists developed for TAAR1, and has been used to demonstrate an important role for TAAR1 in regulation of dopaminergic signalling in the limbic system. Although EPPTB has high affinity for the mouse TAAR1, it has much lower affinity for rat and human TAAR1, which limits its use in research. While the human and mouse forms of TAAR1 have similar functions and bind similar ligands, the actual binding affinities of individual ligands often vary significantly between the two versions of the receptor.
o-Phenyl-3-iodotyramine (o-PIT) is a drug which acts as a selective agonist for the trace amine-associated receptor 1. It has reasonable selectivity for TAAR1 but relatively low potency, and is rapidly metabolised in vivo, making it less useful for research than newer ligands such as RO5166017.