AL-34662 is an

indazole Indazole, also called isoindazole, is a heterocyclic aromatic organic compound. This bicyclic compound consists of the fusion of benzene and pyrazole. Indazole is an amphoteric molecule which can be protonated to an indazolium cation or deproton ...

derivative drug that is being developed for the treatment of

glaucoma Glaucoma is a group of eye diseases that result in damage to the optic nerve (or retina) and cause vision loss. The most common type is open-angle (wide angle, chronic simple) glaucoma, in which the drainage angle for aqueous humor, fluid withi ...

. It acts as a selective 5-HT_2A

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

agonist 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 ag ...

, the same target as that of

psychedelic Psychedelics are a subclass of hallucinogenic drugs whose primary effect is to trigger non-ordinary states of consciousness (known as psychedelic experiences or "trips").Pollan, Michael (2018). ''How to Change Your Mind: What the New Science o ...

drugs like

psilocin Psilocin (also known as 4-HO-DMT, 4-hydroxy DMT, psilocine, psilocyn, or psilotsin) is a substituted tryptamine alkaloid and a serotonergic psychedelic substance. It is present in most psychedelic mushrooms together with its phosphorylated cou ...

, but unlike these drugs, AL-34662 was designed specifically as a peripherally selective drug, which does not cross the

blood–brain barrier The blood–brain barrier (BBB) is a highly selective semipermeable border of endothelial cells that prevents solutes in the circulating blood from ''non-selectively'' crossing into the extracellular fluid of the central nervous system where ne ...

. This means that AL-34662 can exploit a useful side effect of the hallucinogenic 5-HT_2A agonists, namely reduction in intra-ocular pressure and hence relief from the symptoms of glaucoma, but without causing the hallucinogenic effects that make centrally active 5-HT_2A agonists unsuitable for clinical use. In animal studies, 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 5-HT_2A agonists at present, as centrally acting agonists for this receptor tend to be hallucinogenic and thus their medical usefulness is currently limited to the treatment of psychiatric disorders. While many novel, potent and selective 5-HT_2A agonists have been developed for this application, retaining peripheral selectivity can be a problem, and several of the more

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

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

{{Serotonergics Indazoles Amines Peripherally selective drugs Serotonin receptor agonists Hydroxyarenes

See also

References