Skip to main content
Log in

The influence of ipsapirone, a 5-HT1A agonist, on sleep patterns of healthy subjects

  • Original Investigation
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Ipsapirone is a new pyrimidinylpiperazine ligand specific for 5-HT1A receptors, with potential therapeutic use in affective disorders. Because 5-HT is involved in the regulation of sleep, we investigated the effect of ipsapirone hydrochloride on sleep patterns in 18 normal, healthy subjects of both sexes. Compared to placebo, ipsapirone 5 mg administered by mouth three times daily for 14 days decreased rapid eye movement (REM) sleep duration and, by the tenth day of treatment, began to reduce slow wave sleep (SWS) duration. The decrease in REM sleep occurred in the first 3 h of sleep. The latency to REM sleep was increased from the first night following ipsapirone administration, remained increased throughout the 14 days of administration, and fell to equal latency on placebo immediately administration ended. Subjective assessments of sleep revealed no differences between ipsapirone and placebo. Our experiments confirm a role of 5-HT1A receptors in sleep. The effects of ipsapirone on the sleep patterns of patients with affective disorders still need to be determined.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Adrien J (1992) 5-HT receptor ligands and sleep wakefulness regulations. Is there a relationship with their psychotropic actions? J Sleep Res 1:3

    Google Scholar 

  • Agnew HW, Webb WB, Williams RL (1966) The first night effect: an EEG study of sleep. Psychophysiology 2:263–266

    Google Scholar 

  • Benca RM, Obermeyer WH, Thisted RA, Gillin JC (1992) Sleep and psychiatric disorders. A meta-analysis. Arch Gen Psychiatry 49:651–668; discussion 669–670

    Google Scholar 

  • Berger M, Riemann D (1993) REM sleep in depression-an overview. J Sleep Res 2:211–223

    Google Scholar 

  • Bjorvath B, Ursin R (1990) Effects of zimeldine, a selective 5-HT reuptake inhibitor, combined with ritanserin, a selective 5-HT2 antagonist, on waking and sleep stages in rats. Behav Brain Res (Netherlands) 40:239–246

    Google Scholar 

  • Blier P, De Montigny C, Chaput Y (1987) Modifications of the serotonin system by antidepressant treatments: implications for the therapeutic response in major depression. J Clin Psychopharmacol 7:245–355

    Google Scholar 

  • Cespuglio R, Houdouin F, Oulerich M, El Mansari M, Jouvet M (1992) Axonal and somato-dendritic modalities of serotonin release: their involvement in sleep preparation, triggering and maintenance. J Sleep Res 1:150–156

    Google Scholar 

  • Chen C (1979) Sleep, depression, and antidepressants. Br J Psychiatry 135:385–402

    Google Scholar 

  • Cutler NR, Sramek JJ, Wardle TS, Keppel Hesselink JM, Roeschen JK (1993) The safety and efficacy of ipsapirone vs. lorazepam in outpatients with generalized anxiety disorder (GAD): single site findings from a multicenter trial. Psychopharmacol Bull 29:303–308

    Google Scholar 

  • Declerck AC, Wauquier A, Van der Ham-Veltman PHM, Gelders Y (1987) Increase in slow-wave sleep in humans with the serotonin-S2 antagonist ritanserin. Curr Ther Res 41:427–432

    Google Scholar 

  • De Vry J, Glaser T, Traber J (1990) 5HT1A receptor partial agonists as anxiolytics. In: Paoletti R, van Houtte PM, Brunello N, Maggi FM (eds) Serotonin: from cell biology to pharmacology and therapeutics. Kluwer Dortrecht, pp 517–522

  • De Vry JM, Schreiber R, Glaser T, Traber J (1992) Behavioural pharmacology of 5-HT1A agonists: animal models of anxiety and depression. In: Stahl SM, Gastpar M, Keppel Hesselink JM, Traber J (eds) Serotonin 1A receptors in depression and anxiety. Raven Press, New York, pp 55–84

    Google Scholar 

  • Feinberg M, Gillin JC, Carroll BJ (1982) EEG studies of sleep in the diagnosis of depression. Biol Psychiatry 17: 305–317

    Google Scholar 

  • Flanigan MJ, Shapiro CM (1994) Monoamine oxidase inhibitors and sleep. In: Kennedy SH (ed) Clinical advances in monoamine oxidase inhibitor therapies. American Psychiatric Press, Washington, DC (Progress in Psychiatry series #43), pp 125–145

    Google Scholar 

  • Flanigan MJ, Smit L, Driver H, Shapiro C, Laburn H (1990) Does amitriptyline affect sleep and nocturnal temperatures in normal subjects? S Afr J Sci 86:533–534

    Google Scholar 

  • Gardner MJ, Altman DG (1986) Confidence intervals rather thanP-values: estimation rather than hypothesis testing. BMJ 292:746–750

    Google Scholar 

  • General Practice Research Unit (1972) General Health Questionnaire (GHQ 30). NFEF-Nelson, Oxford

    Google Scholar 

  • Gillin JC, Borbély AA (1985) Sleep: a neurobiological window on affective disorders. Trends Neurosci 8:537–542

    Google Scholar 

  • Glaser T, De Vry JM (1992) Neurobiology of 5-HT1A receptors. In: Stahl SM, Gastpar M, Keppel Hesselink JM, Traber J (eds) Serotonin 1A receptors in depression and anxiety. Raven Press, New York, pp 35–54

    Google Scholar 

  • Grahame-Smith DG (1992) An overview of serotonin and psychiatry. In: Stahl SM, Gastpar M, Keppel Hesselink JM, Traber J (eds) Serotonin 1A receptors in depression and anxiety. Raven Press, New York, pp 1–22

    Google Scholar 

  • Idzikowski C, Glennard R, Mills JF (1986) 5-Hydroxytriptamine-2-antagonist increases human slow wave sleep. Brain Res 378:164–168

    Google Scholar 

  • Idzikowski C, Cown PJ, Nutt D, Mills JF (1987) The effects of chronic ritanserin treatment on sleep and the neuroendocrine response tol-tryptophan. Psychopharmacology 93:416–420

    Google Scholar 

  • Jouvet M (1977) Neuropharmacology of the sleep-waking cycle. Handbook of Psychopharmacology 8:233–293

    Google Scholar 

  • Katzung BG (1989) Basic and clinical pharmacology. Prentice Hall, London, p 361

    Google Scholar 

  • Keppel Hesselink JM (1992) Promising anxiolytics? A new class of drugs: The azapirones. In: Stahl SM, Gastpar M, Keppel Hesselink JM, Traber J (eds) Serotonin 1A receptors in depression and anxiety. Raven Press, New York, pp 171–184

    Google Scholar 

  • Kurtz N (1992) Efficacy of azapirones in depression. In: Stahl SM, Gastpar M, Keppel Hesselink JM, Traber J (eds) Serotonin 1A receptors in depression and anxiety. Raven Press, New York, pp 163–170

    Google Scholar 

  • Luus HG, Müller FO, Meyer BH (1989) Statistical significance versus clinical relevance. Part II. The use and interpretation of confidence intervals. S Afr Med J 76:626–629

    Google Scholar 

  • Martin P, Tissier M-H, Adrien J, Puech AJ (1991) Antidepressant-like effects of buspirone mediated by the 5-HT1A post-synaptic receptors in the learned helplessness paradigm. Life Sci 48:2505–2511

    Google Scholar 

  • McGeer PL, Eccles JC, McGeer EG (eds) (1987) Molecular neurobiology of the mammalian brain, 2nd edition. Plenum, New York, pp 319–347, 548–549

    Google Scholar 

  • Mendelson WB, Martin JV, Rapoport DM (1990) Effects of buspirone on sleep and respiration. Am Rev Respir Dis 141:1527–1530

    Google Scholar 

  • Monti JM, Piñeyro G, Orellana C, Boussard M, Jantos H, Labraga P, Olivera S, Alvariño F (1990) 5-HT receptor agonists 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and 8-OH-DPAT increase wakefulness in the rat. Biogen Amines 7:145–151

    Google Scholar 

  • Peroutka SJ (1985) Selective interaction of novel anxiolytics with 5-hydroxytryptamine1A receptors. Biol Psychiatry 20:971–979

    Google Scholar 

  • Rechtschaffen A, Kales A (eds) (1968) A manual of standardized terminology, techniques and scoring system for sleep stages of human subjects. UCLA Brain Information Service, Los Angeles

    Google Scholar 

  • Reynolds CF, Kupfer DJ (1987) Sleep research in affective illness: state of the art circa 1987. Sleep 10:199–215

    Google Scholar 

  • Reynolds CF, Shaw DH, Newton TF, Coble PA, Kupfer DJ (1983) EEG sleep in out- patients with generalized anxiety. A preliminary comparison with depressed outpatients. Psychiatry Res 8:81–89

    Google Scholar 

  • Rowan MJ, Anwyl R (1987) Neurophysiology effects of buspirone and ipsapirone in the hippocampus comparison with 5-hydroxytryptamine. Eur J Pharmacol 132:93–96

    Google Scholar 

  • Ross RJ, Ball WA, Gresch PJ, Morrison AR (1990) REM sleep suppression by monoamine re-uptake blockade: development of tolerance with repeated drug administration. Biol Psychiatry 28:231–239

    Google Scholar 

  • Seidel WF, Cohen SA, Bliwise NG, Dement WC (1985) Buspirone, an anxiolytic without sedative effect. Psychopharmacology 87:371–373

    Google Scholar 

  • Steriade M, McCarley RW (1990) Brainstem control of wakefulness and sleep. Plenum, New York, pp 380–385

    Google Scholar 

  • Tissier M-H, Franc B, Hamon M, Adrien J (1990) Effects of 5-HT1A and 5-HT3 receptor ligands on sleep in the rat. In: Horne J (ed) Sleep '90. Pontenagel Press, Bochum, pp 126–128

    Google Scholar 

  • Tissier M-H, Lainey E, Fattaccini C-M, Hamon M, Adrien J (1993) Effects of ipsapirone, a 5-HT1A agonist, on sleep/wakefulness cycles: probably post-synaptic action. J Sleep Res 2:103–109

    Google Scholar 

  • Tricklebank MD (1987) Sub-types of 5-HT receptors. J Psychopharmacol 1:222–226

    Google Scholar 

  • Trinder J, Stevenson J, Paxton SJ, Montgomery I (1982) Physical fitness, exercise and REM sleep cycle length. Psychophysiology 19:89–93

    Google Scholar 

  • Vogel G (1989) Sleep variables and the treatment of depression. In: Kryger MH, Roth T, Dement WC (eds) Principles and practice of sleep medicine. Saunders, Philadelphia, pp 419–420

    Google Scholar 

  • Walsh JK, Sugerman JL (1989) Disorders of initiating and maintaining sleep in adult psychiatric disorders. In: Kryger MH, Roth T, Dement WC (eds) Principles and practice of sleep medicine. Saunders, Philadelphia, pp 448–455

    Google Scholar 

  • Webb WB, Dreblow LM (1982) The REM cycle, combining rules and age. Sleep 5:372–377

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

Present address: Department of Physiology, University of the Witwatersrand, Medical School, 7 York Road, Parktown 2193, South Africa

Rights and permissions

Reprints and permissions

About this article

Cite this article

Driver, H.S., Flanigan, M.J., Bentley, A.J. et al. The influence of ipsapirone, a 5-HT1A agonist, on sleep patterns of healthy subjects. Psychopharmacology 117, 186–192 (1995). https://doi.org/10.1007/BF02245186

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02245186

Key words

Navigation