Robalzotan

Last updated
Robalzotan
Robalzotan.svg
Clinical data
Other namesNAD-299; NAD299; AZD-371; AZD371
Routes of
administration 		Oral [1]
Drug class Serotonin 5-HT1A receptor antagonist
ATC code
  • None
Legal status
Legal status
  • In general: uncontrolled
Identifiers
  • (3R)-3-[di(cyclobutyl)amino]-8-fluoro-3,4-dihydro-2H-chromene-5-carboxamide
CAS Number
PubChem CID
IUPHAR/BPS
ChemSpider
UNII
CompTox Dashboard (EPA)
Chemical and physical data
Formula C18H23FN2O2
Molar mass 318.392 g·mol−1
3D model (JSmol)
  • C1CC(C1)N(C2CCC2)[C@@H]3CC4=C(C=CC(=C4OC3)F)C(=O)N
  • InChI=1S/C18H23FN2O2/c19-16-8-7-14(18(20)22)15-9-13(10-23-17(15)16)21(11-3-1-4-11)12-5-2-6-12/h7-8,11-13H,1-6,9-10H2,(H2,20,22)/t13-/m1/s1 X mark.svgN
  • Key:MQTUXRKNJYPMCG-CYBMUJFWSA-N X mark.svgN
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Robalzotan (INN Tooltip International Nonproprietary Name, BAN Tooltip 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.
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