Ipsapirone
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Antidepressant and anxiolytic drug
Pharmaceutical compound
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| Other names | BAY Q 7821; BAY-Q-7821; TVX Q 7821; TVX-Q-7821 |
| Routes of administration | Oral [1] |
| Drug class | Serotonin 5-HT1A receptor partial agonist |
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| Metabolites | 1-(2-Pyrimidinyl)piperazine (1-PP) (2%)[2] |
| Elimination half-life | Ipsapirone: 1–3 hours[3] [4] [2] 1-PP: 6.1hours[2] |
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| Formula | C19H23N5O3S |
| Molar mass | 401.49g·mol−1 |
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Ipsapirone (INN Tooltip International Nonproprietary Name, USAN Tooltip United States Adopted Name, BAN Tooltip British Approved Name; developmental code names BAY Q 7821 and TVX Q 7821) is a selective 5-HT1A receptor partial agonist of the arylpiperazine and azapirone families which was under development for the treatment of major depressive disorder and anxiety disorders but was never marketed.[1] [5] It is taken orally.[1]
The drug produces antidepressant-like, anxiolytic-like, and antiaggressive effects in rodents.[5] [6] It has been found to increase oxytocin levels in rodents,[7] [8] [9] [10] whereas findings in humans have been mixed.[11] [12] Ipsapirone produces adverse effects including vertigo, dizziness, and dysphoria in humans.[3]
Ipsapirone produces 1-(2-pyrimidinyl)piperazine (1-PP), a potent α2-adrenergic receptor antagonist, as an active metabolite.[2] However, whereas 1-PP levels with buspirone are 8-fold higher than levels of buspirone itself, 1-PP is only a minor metabolite of ipsapirone constituting 2% of its exposure.[2]
Ipsapirone was first described in the scientific literature by 1984.[13] [14] It was developed by Bayer.[1] The drug reached phase 3 clinical trials for treatment of major depressive disorder prior to the discontinuation of its development in 1997.[1] It was also studied for treatment of generalized anxiety disorder.[15]
See also
[edit ]References
[edit ]- 1 2 3 4 5 "Ipsapirone". AdisInsight. 3 January 1997. Retrieved 24 July 2026.
- 1 2 3 4 5 Berlin I, Chalon S, Payan C, Schöllnhammer G, Cesselin F, Varoquaux O, Puech AJ (March 1995). "Evaluation of the alpha 2-adrenoceptor blocking properties of buspirone and ipsapirone in healthy subjects. Relationship with the plasma concentration of the common metabolite 1-(2-pyrimidinyl)-piperazine". Br J Clin Pharmacol. 39 (3): 243–249. doi:10.1111/j.1365-2125.1995.tb04443.x. PMC 1364998 . PMID 7619663.
In humans plasma levels of 1PP after administration of buspirone are eightfold greater on a molar basis than that of buspirone [9]. Peak plasma concentration of 1PP after oral administration of 20 mg buspirone is attained in 30-60 min and its elimination half-life is 6.1 ± 0.3 h, twice as high as that of buspirone and varies little among subjects [3]. [...] After oral administration of ipsapirone to healthy subjects, time to peak plasma concentration is reached within 0.5 to 1.3 h, its elimination half-life is about 2 h. Steady state concentrations are obtained after 3 days. Ipsapirone is nearly completely metabolised by the liver and IPP is only a minor metabolite of ipsapirone (2% of the dose given) [12].
- 1 2 Fuhr U, Staib AH, Harder S, Becker K, Liermann D, Schöllnhammer G, Roed IS (July 1994). "Absorption of ipsapirone along the human gastrointestinal tract". Br J Clin Pharmacol. 38 (1): 83–86. doi:10.1111/j.1365-2125.1994.tb04327.x. PMC 1364843 . PMID 7946942.
In man, ipsapirone has an absorption half-life of less than 0.25 h and an elimination half-life ranging from 1-3 h [4, 5]. The rapid increase of its plasma concentration following oral administration in solution is often accompanied by vertigo, dizziness and dysphoria [5], effects which should be avoided by formulating the drug in a modified release preparation.
- ↑ Schöllnhammer G. Pharmacokinetics of the azapirones. In Serotonin 1A receptors in depression and anxiety, eds Gastpar M, et al. New York: Raven Press Ltd, 1992; 99–107. https://scholar.google.com/scholar?cluster=11279309651232496395
- 1 2 Fanelli RJ, Schuurman T, Glaser T, Traber J (1990). "Ipsapirone: a novel anxiolytic and selective 5-HT1A receptor ligand". Progress in Clinical and Biological Research. 361: 461–467. PMID 1981264.
- ↑ de Boer SF, Koolhaas JM (December 2005). "5-HT1A and 5-HT1B receptor agonists and aggression: a pharmacological challenge of the serotonin deficiency hypothesis". Eur J Pharmacol. 526 (1–3): 125–139. doi:10.1016/j.ejphar.2005年09月06日5. PMID 16310183.
- ↑ Bagdy G, Kalogeras KT (May 1993). "Stimulation of 5-HT1A and 5-HT2/5-HT1C receptors induce oxytocin release in the male rat". Brain Res. 611 (2): 330–332. doi:10.1016/0006-8993(93)90521-n. PMID 8334526.
- ↑ Li Q, Brownfield MS, Levy AD, Battaglia G, Cabrera TM, Van de Kar LD (September 1994). "Attenuation of hormone responses to the 5-HT1A agonist ipsapirone by long-term treatment with fluoxetine, but not desipramine, in male rats". Biol Psychiatry. 36 (5): 300–308. doi:10.1016/0006-3223(94)90627-0. PMID 7993956.
- ↑ Bagdy G (1996). "Role of the hypothalamic paraventricular nucleus in 5-HT1A, 5-HT2A and 5-HT2C receptor-mediated oxytocin, prolactin and ACTH/corticosterone responses". Behav Brain Res. 73 (1–2): 277–280. doi:10.1016/0166-4328(96)00112-x. PMID 8788518.
- ↑ Bagdy G (1996). "Studies on the sites and mechanisms of 5-HT1A receptor-mediated in vivo actions". Acta Physiol Hung. 84 (4): 399–401. PMID 9328612.
- ↑ Cleare AJ, Forsling M, Bond AJ (January 1998). "Neuroendocrine and hypothermic effects of 5-HT1A receptor stimulation with ipsapirone in healthy men: a placebo-controlled study". Int Clin Psychopharmacol. 13 (1): 23–32. doi:10.1097/00004850-199801000-00004. PMID 9988364.
- ↑ Newman ME, Li Q, Gelfin Y, Van de Kar LD, Lerer B (July 1999). "Low doses of ipsapirone increase growth hormone but not oxytocin secretion in normal male and female subjects". Psychopharmacology (Berl). 145 (1): 99–104. doi:10.1007/s002130051037. PMID 10445378.
- ↑ Traber J, Davies MA, Dompert WU, Glaser T, Schuurman T, Seidel PR (June 1984). "Brain serotonin receptors as a target for the putative anxiolytic TVX Q 7821". Brain Res Bull. 12 (6): 741–744. doi:10.1016/0361-9230(84)90155-2. PMID 6541079.
- ↑ Dompert WU, Glaser T, Traber J (February 1985). "3H-TVX Q 7821: identification of 5-HT1 binding sites as target for a novel putative anxiolytic". Naunyn Schmiedebergs Arch Pharmacol. 328 (4): 467–470. doi:10.1007/BF00692918. PMID 2859533.
- ↑ Chessick CA, Allen MH, Thase M, Batista Miralha da Cunha AB, Kapczinski FF, de Lima MS, dos Santos Souza JJ (July 2006). "Azapirones for generalized anxiety disorder". The Cochrane Database of Systematic Reviews. 2006 (3) CD006115. doi:10.1002/14651858.CD006115. PMC 8915394 . PMID 16856115.