Robalzotan (INNTooltip International Nonproprietary Name, BANTooltip British Approved Name; 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.[2][3][4][5]

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.[6]

The drug was investigated by AstraZeneca as a potential antidepressant, but like many other serotonin 5-HT1A receptor modulators, was discontinued.[7] Later on, it was also researched for other indications, such as IBS, but was dropped once again due to lack of effectiveness[3] as well as a poor tolerability profile, which included effects such as "hallucinations or hallucination-like adverse events".[1]

See also

References

  1. 1 2 Drossman DA, Danilewitz M, Naesdal J, Hwang C, Adler J, Silberg DG (October 2008). "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. doi:10.1111/j.1572-0241.2008.02115.x. PMID 18775020.
  2. ↑ "Robalzotan - AdisInsight". adisinsight.springer.com. Retrieved 27 February 2026.
  3. 1 2 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. 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).
  4. ↑ Jerning E, Svantesson GT, Mohell N (1998). "Receptor binding characteristics of [3H]NAD-299, a new selective 5-HT1A receptor antagonist". Eur J Pharmacol. 360 (2–3): 219–225. doi:10.1016/S0014-2999(98)00667-0. PMID 9851589.
  5. ↑ Andrée B, Hedman A, Thorberg SO, Nilsson D, Halldin C, Farde L (April 2003). "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. doi:10.1007/s00213-002-1355-0. PMID 12632244.
  6. ↑ Arborelius L, Wallsten C, Ahlenius S, Svensson TH (1999). "The 5-HT(1A) receptor antagonist robalzotan completely reverses citalopram-induced inhibition of serotonergic cell firing". Eur J Pharmacol. 382 (2): 133–138. doi:10.1016/S0014-2999(99)00592-0. PMID 10528148.
  7. ↑ Mucke HA (2000). "Robalzotan AstraZeneca". Curr Opin Investig Drugs. 1 (2): 236–240. PMID 11249580.
source: https://en.wikipedia.org/wiki/Robalzotan