Adenosine (symbol A or Ado) is an organic compound that occurs widely in nature in the form of diverse derivatives. The molecule consists of an adenine attached to a ribose via a β-N9-glycosidic bond. Adenosine is one of four nucleoside building blocks to DNA and RNA, which are essential for all life. Its derivatives include the energy carriers adenosine mono-, di-, and triphosphate, also known as AMP/ADP/ATP.
An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the agonist, while an inverse agonist causes an action opposite to that of the agonist.
A receptor antagonist is a type of receptor ligand or drug that blocks or dampens a biological response by binding to and blocking a receptor rather than activating it like an agonist. Antagonist drugs interfere in the natural operation of receptor proteins. They are sometimes called blockers; examples include alpha blockers, beta blockers, and calcium channel blockers. In pharmacology, antagonists have affinity but no efficacy for their cognate receptors, and binding will disrupt the interaction and inhibit the function of an agonist or inverse agonist at receptors. Antagonists mediate their effects by binding to the active site or to the allosteric site on a receptor, or they may interact at unique binding sites not normally involved in the biological regulation of the receptor's activity. Antagonist activity may be reversible or irreversible depending on the longevity of the antagonist–receptor complex, which, in turn, depends on the nature of antagonist–receptor binding. The majority of drug antagonists achieve their potency by competing with endogenous ligands or substrates at structurally defined binding sites on receptors.
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.
In pharmacology, an inverse agonist is a drug that binds to the same receptor as an agonist but induces a pharmacological response opposite to that of the agonist.
Aminophylline is a compound of the bronchodilator theophylline with ethylenediamine in 2:1 ratio. The ethylenediamine improves solubility, and the aminophylline is usually found as a dihydrate.
The adenosine A1 receptor is one member of the adenosine receptor group of G protein-coupled receptors with adenosine as endogenous ligand.
The 5-HT2A receptor is a subtype of the 5-HT2 receptor that belongs to the serotonin receptor family and is a G protein-coupled receptor (GPCR). The 5-HT2A receptor is a cell surface receptor, but has several intracellular locations. 5-HT is short for 5-hydroxy-tryptamine or serotonin. This is the main excitatory receptor subtype among the GPCRs for serotonin, although 5-HT2A may also have an inhibitory effect on certain areas such as the visual cortex and the orbitofrontal cortex. This receptor was first noted for its importance as a target of serotonergic psychedelic drugs such as LSD and psilocybin mushrooms. Later it came back to prominence because it was also found to be mediating, at least partly, the action of many antipsychotic drugs, especially the atypical ones.
Growth hormone secretagogue receptor(GHS-R), also known as ghrelin receptor, is a G protein-coupled receptor that binds growth hormone secretagogues (GHSs), such as ghrelin, the "hunger hormone". The role of GHS-R is thought to be in regulating energy homeostasis and body weight. In the brain, they are most highly expressed in the hypothalamus, specifically the ventromedial nucleus and arcuate nucleus. GSH-Rs are also expressed in other areas of the brain, including the ventral tegmental area, hippocampus, and substantia nigra. Outside the central nervous system, too, GSH-Rs are also found in the liver, in skeletal muscle, and even in the heart.
FG-7142 (ZK-31906) is a drug which acts as a partial inverse agonist at the benzodiazepine allosteric site of the GABAA receptor. It has anorectic, anxiogenic and pro-convulsant effects. It also increases release of acetylcholine and noradrenaline, and improves memory retention in animal studies.
The adenosine A2A receptor, also known as ADORA2A, is an adenosine receptor, and also denotes the human gene encoding it.
The adenosine A3 receptor, also known as ADORA3, is an adenosine receptor, but also denotes the human gene encoding it.
The adenosine A2B receptor, also known as ADORA2B, is a G-protein coupled adenosine receptor, and also denotes the human adenosine A2b receptor gene which encodes it.
8-Cyclopentyl-1,3-dipropylxanthine (DPCPX, PD-116,948) is a drug which acts as a potent and selective antagonist for the adenosine A1 receptor. It has high selectivity for A1 over other adenosine receptor subtypes, but as with other xanthine derivatives DPCPX also acts as a phosphodiesterase inhibitor, and is almost as potent as rolipram at inhibiting PDE4. It has been used to study the function of the adenosine A1 receptor in animals, which has been found to be involved in several important functions such as regulation of breathing and activity in various regions of the brain, and DPCPX has also been shown to produce behavioural effects such as increasing the hallucinogen-appropriate responding produced by the 5-HT2A agonist DOI, and the dopamine release induced by MDMA, as well as having interactions with a range of anticonvulsant drugs.
A cannabinoid receptor antagonist, also known simply as a cannabinoid antagonist or as an anticannabinoid, is a type of cannabinoidergic drug that binds to cannabinoid receptors (CBR) and prevents their activation by endocannabinoids. They include antagonists, inverse agonists, and antibodies of CBRs. The discovery of the endocannabinoid system led to the development of CB1 receptor antagonists. The first CBR inverse agonist, rimonabant, was described in 1994. Rimonabant blocks the CB1 receptor selectively and has been shown to decrease food intake and regulate body-weight gain. The prevalence of obesity worldwide is increasing dramatically and has a great impact on public health. The lack of efficient and well-tolerated drugs to cure obesity has led to an increased interest in research and development of CBR antagonists. Cannabidiol (CBD), a naturally occurring cannabinoid, is a non-competitive CB1/CB2 receptor antagonist. And Δ9-tetrahydrocannabivarin (THCV), a naturally occurring cannabinoid, modulate the effects of THC via direct blockade of cannabinoid CB1 receptors, thus behaving like first-generation CB1 receptor inverse agonists, such as rimonabant. CBD is a very low-affinity CB1 ligand, that can nevertheless affect CB1 receptor activity in vivo in an indirect manner, while THCV is a high-affinity CB1 receptor ligand and potent antagonist in vitro and yet only occasionally produces effects in vivo resulting from CB1 receptor antagonism. THCV has also high affinity for CB2 receptors and signals as a partial agonist, differing from both CBD and rimonabant.
BAY 60–6583 is a selective adenosine A2B receptor agonist. It has been shown to provide protection from ischemia in both the heart and kidney of test animals, and has also been shown to be beneficial in treatment of acute lung and brain injury, as well as claimed anti-aging and anti-obesity effects, showing a range of potential applications for selective A2B agonists.
SB-269970 is a drug and research chemical developed by GlaxoSmithKline used in scientific studies. It is believed to act as a selective 5-HT7 receptor antagonist (EC50 = 1.25 nM) (or possibly inverse agonist). A subsequent study in guinea pig at a concentration of 10 μM showed that it also blocks the α2-adrenergic receptor. The large difference in test concentrations however confirms the selectivity of SB-269970 for the 5-HT7 receptor.
PSB-10 is a drug which acts as a selective antagonist for the adenosine A3 receptor (ki value at human A3 receptor is 0.44 nM), with high selectivity over the other three adenosine receptor subtypes (ki values at human A1, A2A and A2B receptors are 4.1, 3.3 and 30 μM). Further pharmacological experiments in a [35S]GTPγS binding assay using hA3-CHO-cells indicated that PSB-10 acts as an inverse agonist (IC50 = 4 nM). It has been shown to produce antiinflammatory effects in animal studies. Simple xanthine derivatives such as caffeine and DPCPX have generally low affinity for the A3 subtype and must be extended by expanding the ring system and adding an aromatic group to give high A3 affinity and selectivity. The affinity towards adenosine A3 subtype was measured against the radioligand PSB-11.
N6-Cyclopentyladenosine (CPA) is a drug which acts as a selective adenosine A1 receptor agonist. It has mainly cardiovascular effects with only subtle alterations of behavior. CPA is widely used in scientific research into the adenosine receptors and has been used to derive a large family of derivatives.
SB-243213 is a research chemical which acts as a selective inverse agonist for the 5HT2C receptor and has anxiolytic effects. It has better than 100x selectivity for 5-HT2C over all other receptor subtypes tested, and a longer duration of action compared to older 5-HT2C antagonist ligands.
