AL-34662 is an indazole

derivative In mathematics, the derivative is a fundamental tool that quantifies the sensitivity to change of a function's output with respect to its input. The derivative of a function of a single variable at a chosen input value, when it exists, is t ...

drug A drug is any chemical substance other than a nutrient or an essential dietary ingredient, which, when administered to a living organism, produces a biological effect. Consumption of drugs can be via insufflation (medicine), inhalation, drug i ...

that is being developed for the treatment of

glaucoma Glaucoma is a group of eye diseases that can lead to damage of the optic nerve. The optic nerve transmits visual information from the eye to the brain. Glaucoma may cause vision loss if left untreated. It has been called the "silent thief of ...

. It acts as a selective

serotonin Serotonin (), also known as 5-hydroxytryptamine (5-HT), is a monoamine neurotransmitter with a wide range of functions in both the central nervous system (CNS) and also peripheral tissues. It is involved in mood, cognition, reward, learning, ...

5-HT₂

receptor Receptor may refer to: * Sensory receptor, in physiology, any neurite structure that, on receiving environmental stimuli, produces an informative nerve impulse *Receptor (biochemistry), in biochemistry, a protein molecule that receives and respond ...

agonist An agonist is a chemical that activates a Receptor (biochemistry), receptor to produce a biological response. Receptors are Cell (biology), cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an R ...

, including of the 5-HT_2A, 5-HT_2B, and 5-HT_2C receptors (

affinity Affinity may refer to: Commerce, finance and law * Affinity (law), kinship by marriage * Affinity analysis, a market research and business management technique * Affinity Credit Union, a Saskatchewan-based credit union * Affinity Equity Pa ...

() = 14.5, 8.1, and 3.0nM, respectively). The serotonin 5-HT_2A receptor is the same

target Target may refer to: Warfare and shooting * Shooting target, used in marksmanship training and various shooting sports ** Bullseye (target), the goal one for which one aims in many of these sports ** Aiming point, in field artille ...

as that of psychedelic drugs like

psilocin Psilocin, also known as 4-hydroxy-''N'',''N''-dimethyltryptamine (4-HO-DMT), is a substituted tryptamine alkaloid and a serotonergic psychedelic. It is present in most psychedelic mushrooms together with its phosphorylated counterpart psilocy ...

. Unlike these drugs however, AL-34662 was designed specifically as a

peripherally selective drug Peripherally selective drugs have their primary mechanism of action outside of the central nervous system (CNS), usually because they are excluded from the CNS by the blood–brain barrier. By being excluded from the CNS, drugs may act on the rest o ...

, which does not cross the

blood–brain barrier The blood–brain barrier (BBB) is a highly selective semipermeable membrane, semipermeable border of endothelium, endothelial cells that regulates the transfer of solutes and chemicals between the circulatory system and the central nervous system ...

. This means that AL-34662 can exploit a useful

side effect In medicine, a side effect is an effect of the use of a medicinal drug or other treatment, usually adverse but sometimes beneficial, that is unintended. Herbal and traditional medicines also have side effects. A drug or procedure usually use ...

of the hallucinogenic 5-HT_2A receptor agonists, namely reduction in

intra-ocular pressure Intraocular pressure (IOP) is the fluid pressure inside the eye. Tonometry is the method eye care professionals use to determine this. IOP is an important aspect in the evaluation of patients at risk of glaucoma. Most tonometers are calibrated ...

and hence relief from the symptoms of glaucoma, but without causing the psychedelic effects that make centrally active serotonin 5-HT_2A receptor agonists unsuitable for clinical use. In

animal studies Animal studies is a recently recognised field in which animals are studied in a variety of cross-disciplinary ways. Scholars who engage in animal studies may be formally trained in a number of diverse fields, including art history, anthropology ...

, AL-34662 has been shown to be potent and effective in the treatment of symptoms of glaucoma, with minimal side effects. Peripherally acting 5-HT_2A agonists have been a rich field of research in recent years, with potential glaucoma treatments being the main proposed application for serotonin 5-HT_2A receptor agonists at present, as centrally acting agonists for this receptor tend to be

hallucinogen Hallucinogens, also known as psychedelics, entheogens, or historically as psychotomimetics, are a large and diverse class of psychoactive drugs that can produce altered states of consciousness characterized by major alterations in thought, mo ...

ic and thus their medical usefulness is currently limited to the treatment of

psychiatric disorder A mental disorder, also referred to as a mental illness, a mental health condition, or a psychiatric disability, is a behavioral or mental pattern that causes significant distress or impairment of personal functioning. A mental disorder is ...

s. While many novel, potent, and selective serotonin 5-HT_2A receptor agonists have been developed for this application, retaining peripheral selectivity can be a problem, and several of the more

lipophilic Lipophilicity (from Greek language, Greek λίπος "fat" and :wikt:φίλος, φίλος "friendly") is the ability of a chemical compound to dissolve in fats, oils, lipids, and non-polar solvents such as hexane or toluene. Such compounds are c ...

compounds closely related to AL-34662 such as those shown below, did cross the blood–brain barrier and produced hallucinogen-appropriate responding in animals. :

References

{{Serotonin receptor modulators 5-HT2B agonists 5-HT2C agonists Amines Hydroxyarenes Indazoles Non-hallucinogenic 5-HT2A receptor agonists Peripherally selective drugs

See also

References