The adenosine receptors (or P1 receptors) are a class of purinergic G protein-coupled receptors with adenosine as the endogenous ligand. There are four known types of adenosine receptors in humans: A1, A2A, A2B and A3; each is encoded by a different gene.
Tetrabenazine is a drug for the symptomatic treatment of hyperkinetic movement disorders. It is sold under the brand names Nitoman and Xenazine among others. On August 15, 2008, the U.S. Food and Drug Administration approved the use of tetrabenazine to treat chorea associated with Huntington's disease. Although other drugs had been used "off label," tetrabenazine was the first approved treatment for Huntington's disease in the U.S. The compound has been known since the 1950s.
Nomifensine, sold under the brand names Merital and Alival, is a norepinephrine–dopamine reuptake inhibitor (NDRI), i.e. a drug that increases the amount of synaptic norepinephrine and dopamine available to receptors by blocking the dopamine and norepinephrine reuptake transporters. This is a mechanism of action shared by some recreational drugs like cocaine and the medication tametraline (see DRI). Research showed that the (S)-isomer is responsible for activity.
The adenosine A2A receptor, also known as ADORA2A, is an adenosine receptor, and also denotes the human gene encoding it.
SCH-58261 is a drug which acts as a potent and selective antagonist for the adenosine receptor A2A, with more than 50x selectivity for A2A over other adenosine receptors. It has been used to investigate the mechanism of action of caffeine, which is a mixed A1 / A2A antagonist, and has shown that the A2A receptor is primarily responsible for the stimulant and ergogenic effects of caffeine, but blockade of both A1 and A2A receptors is required to accurately replicate caffeine's effects in animals. SCH-58261 has also shown antidepressant, nootropic and neuroprotective effects in a variety of animal models, and has been investigated as a possible treatment for Parkinson's disease.
Istradefylline, sold under the brand name Nourianz, is a medication used as an add-on treatment to levodopa/carbidopa in adults with Parkinson's disease (PD) experiencing "off" episodes. Istradefylline reduces "off" periods resulting from long-term treatment with the antiparkinson drug levodopa. An "off" episode is a time when a patient's medications are not working well, causing an increase in PD symptoms, such as tremor and difficulty walking.
Preladenant is a drug that was developed by Schering-Plough which acted as a potent and selective antagonist of the adenosine A2A receptor. It was being researched as a potential treatment for Parkinson's disease. Positive results were reported in Phase II clinical trials in humans, but it did not prove itself to be more effective than a placebo during Phase III trials, and so was discontinued in May 2013.
CE-123, or as the active enantiomer (S)-CE-123, is an analog of modafinil, the most researched of a series of structurally related heterocyclic derivatives. In animal studies, CE-123 was found to improve performance on tests of learning and memory in a manner consistent with a nootropic effect profile. (S)-CE-123 has pro-motivational effects in animals, reverses tetrabenazine-induced motivational deficits, and could be useful in the treatment of motivational disorders in humans.
Monoamine-depleting agents are a group of drugs which reversibly deplete one or more of the monoamine neurotransmitters, serotonin, dopamine, and norepinephrine. One mechanism by which these agents act is by inhibiting reuptake by the vesicular monoamine transporters, VMAT1 and VMAT2. Examples of monoamine-depleting agents include deutetrabenazine, oxypertine, reserpine, tetrabenazine, and valbenazine. Tetrabenazine selectively depletes dopamine at low doses and is used as an animal model of amotivation.
PRX-14040 is a selective dopamine reuptake inhibitor that was developed by Prexa Pharmaceuticals. It has 28-fold selectivity for the dopamine transporter over the norepinephrine transporter. Similarly to various other dopamine reuptake inhibitors, the drug has been found to reverse motivational deficits induced by the dopamine depleting agent tetrabenazine in animals.
MRZ-9547, also known as (R)-phenylpiracetam, (R)-phenotropil, or (R)-fonturacetam, is a selective dopamine reuptake inhibitor (IC50Tooltip half-maximal inhibitory concentration = 14.5 μM) that was developed by Merz Pharma. It is the (R)-enantiomer of the racetam and nootropic phenylpiracetam (phenotropil; fonturacetam).
A pro-motivational agent is a drug which increases motivation. They can be used in the treatment of motivational deficits, for instance in depression, schizophrenia, and attention deficit hyperactivity disorder (ADHD), as well as in the treatment of disorders of diminished motivation (DDMs), including apathy, abulia, and akinetic mutism, for instance due to stroke, traumatic brain injury, or neurodegenerative diseases. They are also used non-medically by healthy people to increase motivation and productivity, for instance in educational contexts.
JJC8-091 is an atypical dopamine reuptake inhibitor (DRI) that was derived from modafinil. It is a lead compound for potential treatment of psychostimulant use disorder (PSUD) and is under development by Encepheal Therapeutics for use as a pharmaceutical drug.
JJC8-089 is a dopamine reuptake inhibitor (DRI) that was derived from modafinil and is related to JJC8-016, JJC8-088, and JJC8-091. Its affinity (Ki) for the dopamine transporter (DAT) is 37.8 nM, for the norepinephrine transporter (NET) is 11,820 nM, for the serotonin transporter (SERT) is 6,800 nM, and for the sigma σ1 receptor is 2.24 nM. It also has significant affinity for several dopamine receptors. JJC8-089 has substantially higher affinity for the DAT than modafinil. The drug shows pro-motivational effects in animals. It was first described in the scientific literature by 2016.
Lu AA47070 is a selective adenosine A2A receptor antagonist that was under development for the treatment of Parkinson's disease but was never marketed. It has been found to reverse some of the effects of dopamine D2 receptor antagonists like pimozide and haloperidol, for instance tremulous jaw movements, catalepsy, locomotor suppression, and other anti-motivational effects, in animals. The drug is a prodrug of Lu AA41063. It was discontinued in phase 1 clinical trials because it lacked the intended pharmacological properties in humans. Lu AA47070 was first described by 2008.
MSX-3 is a selective adenosine A2A receptor antagonist used in scientific research. Similarly to MSX-4, it is a water-soluble ester prodrug of MSX-2.
3-Chlorostyrylcaffeine (CSC), or 8-(3-chlorostyryl)caffeine (8-CSC), is a potent and selective adenosine A2A receptor antagonist which is used in scientific research.
MSX-2 is a selective adenosine A2A receptor antagonist used in scientific research. It is a xanthine and a derivative of the non-selective adenosine receptor antagonist caffeine.
Lu AA41063 is a selective adenosine A2A receptor antagonist. Structurally, it is a non-xanthine.
