AL-34662

AL-34662 is an indazole derivative drug that is being developed for the treatment of glaucoma. It acts as a selective serotonin 5-HT₂ receptor agonist, including of the 5-HT_2A, 5-HT_2B, and 5-HT_2C receptors (affinity (IC₅₀Tooltip half-maximal inhibitory concentration) = 14.5, 8.1, and 3.0 nM, respectively). The serotonin 5-HT_2A receptor is the same target as that of psychedelic drugs like psilocin. Unlike these drugs however, AL-34662 was designed specifically as a peripherally selective drug, which does not cross the blood–brain barrier. This means that AL-34662 can exploit a useful side effect of the hallucinogenic 5-HT_2A receptor agonists, namely reduction in intra-ocular pressure 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, 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 hallucinogenic and thus their medical usefulness is currently limited to the treatment of psychiatric disorders. 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 compounds closely related to AL-34662 such as those shown below, did cross the blood–brain barrier and produced hallucinogen-appropriate responding in animals.