Chemistry:Robalzotan

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Robalzotan (INN, BAN; developmental code names NAD-299, AZD-7371) is a selective antagonist at the serotonin 5-HT1A receptor which was under development for the treatment of major depressive disorder, anxiety disorders, gastrointestinal disorders, irritable bowel syndrome (IBS), and overactive bladder.[1][2][3][4]

It was shown to completely reverse the autoreceptor-mediated inhibition of serotonin release induced by the administration of selective serotonin reuptake inhibitors (SSRIs) like citalopram in rodent studies.[5]

The drug was investigated by AstraZeneca as a potential antidepressant, but like many other serotonin 5-HT1A receptor modulators, was discontinued.[6] Later on, it was also researched for other indications, such as IBS, but was dropped once again due to lack of effectiveness[2] as well as a poor tolerability profile, which included effects such as "hallucinations or hallucination-like adverse events".[7]

See also

References

  1. ↑ "Robalzotan - AdisInsight". https://adisinsight.springer.com/drugs/800006370. 
  2. ↑ 2.0 2.1 Marek, Gerard J. (21 November 2017). "Developing Serotonergic Antidepressants Acting on More Than the Serotonin Transporter". Methods and Principles in Medicinal Chemistry. Wiley. p. 335–367. doi:10.1002/9783527674381.ch12. ISBN 978-3-527-33538-1. https://onlinelibrary.wiley.com/doi/10.1002/9783527674381.ch12. Retrieved 27 February 2026. "Several selective 5-HT1A receptor antagonists have also been synthesized and tested in the clinic [15]. Robalzotan (NAD-299 or AZD 7371) is a 5-HT1A receptor antagonist with over approximately 250-fold greater selectivity at this site compared with other serotonergic and non-serotonergic receptors [100]. Informing phase 2 dose selection, a PET neuroimaging study demonstrated that a single 10 mg oral dose appeared to occupy ∼62–85% and 68–75% of midbrain dorsal raphe and cortical 5-HT1A receptors [101]. Robalzotan monotherapy (5, 10, and 20 mg bid) was tested in 385 patients with MDD in a randomized, double-blind, placebo-controlled, paroxetine-controlled study [102]. Robalzotan did not possess antidepressant activity in this study, even for a post hoc test in those centers demonstrating a 2-point improvement on the HAMD scale for paroxetine compared with placebo (Tables 12.1 and 12.2)." 
  3. ↑ "Receptor binding characteristics of [3H]NAD-299, a new selective 5-HT1A receptor antagonist.". Eur J Pharmacol 360 (2–3): 219–225. 1998. doi:10.1016/S0014-2999(98)00667-0. PMID 9851589. 
  4. ↑ "Positron emission tomographic analysis of dose-dependent NAD-299 binding to 5-hydroxytryptamine-1A receptors in the human brain". Psychopharmacology (Berl) 167 (1): 37–45. April 2003. doi:10.1007/s00213-002-1355-0. PMID 12632244. 
  5. ↑ "The 5-HT(1A) receptor antagonist robalzotan completely reverses citalopram-induced inhibition of serotonergic cell firing.". Eur J Pharmacol 382 (2): 133–138. 1999. doi:10.1016/S0014-2999(99)00592-0. PMID 10528148. 
  6. ↑ Mucke HA (2000). "Robalzotan AstraZeneca.". Curr Opin Investig Drugs 1 (2): 236–240. PMID 11249580. 
  7. ↑ "Randomized, double-blind, placebo-controlled trial of the 5-HT1A receptor antagonist AZD7371 tartrate monohydrate (robalzotan tartrate monohydrate) in patients with irritable bowel syndrome". The American Journal of Gastroenterology 103 (10): 2562–9. October 2008. doi:10.1111/j.1572-0241.2008.02115.x. PMID 18775020. 



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