Abstract
We have compared the cognitive, EEG, and neuroendocrine effects of single doses of umespirone (20 mg and 80 mg) with those of buspirone (30 mg) and placebo in double-blind, cross-over studies in 44 healthy men.
The pattern and time-course of the cognitive effects with umespirone and buspirone were dissimilar. Peak effects of buspirone were seen shortly after dosing and then receded, whilst the effects of umespirone persisted for up to 23 h. Although both drugs objectively impaired attention, buspirone reduced subjective alertness, calmness, and contentedness, whilst umespirone increased subjective alertness and contentedness and showed potential to improve secondary verbal memory.
The EEG effects of umespirone were different from those seen with buspirone; they included a decrease of power in the alpha1 band and the beta bands in the frontocentral area and an increase in the delta and theta bands in the occipitotemporal area. Umespirone had a later onset of action than buspirone but its effects lasted longer.
Similar transient increases in serum prolactin and growth hormone concentrations were seen with buspirone and 80 mg umespirone; umespirone 20 mg had no effect. Plasma concentrations of ACTH and adrenaline and serum concentrations of cortisol were unaffected by either dose of umespirone. There was some evidence that buspirone increased ACTH and cortisol concentrations in some cases, and that umespirone increased noradrenaline concentrations.
The frequency of adverse events was higher with buspirone than with 80 mg of umespirone. At the lower dose of umespirone, the frequency was similar to that with placebo.
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References
Anderson IA, Cowan PJ, Grahame-Smith DG (1990) The effects of gepirone on neuroendocrine function and temperature in humans. Psychopharmacology 100: 498–503
Barnes NM, Costall B, Domeney AM, Gerrard PA, Kelly ME, Krähling H, Naylor RJ, Tomkins DM, Williams TJ (1991) The effects of umespirone as a potential anxiolytic and antipsychotic agent. Pharmacol Biochem Behav 40: 89–96
Blom MW, Bartel PR, Sommers DK, Van der Meyden CH, Becker PJ (1992) The comparison of the effects of multi and single doses of buspirone, chlordiazepoxide and hydroxyzine on psychomotor function and EEG. Fundam Clin Pharmacol 6: 5–9
Bond A, Lader M (1974) The use of analogue scales in rating subjective feelings. Br J Med Psychol 80: 1–46
Bradford LD, Dietrich B, Gerritsen van der Hoop R (1990) The effects of flesinoxan, a new 5-HT1A-agonist, in healthy volunteers on pharmaco-EEG, psychometric tests and neurohormonal parameters. Annual Meeting of the British Association of Psychopharmacology, Cambridge
Checkley SA (1980) Neuroendocrine tests of monoamine function in man: a review of basic theory and its application to the study of depressive illness. Psychol Medicine 10: 35–53
Cowen PJ, Anderson IM, Grahame-Smith D-G (1990 a) Neuroendocrine effects of azapirones. J Clin Psychopharmacol 10: 21 S-25 S
Cowen PJ, Anderson IM, Gartside SE (1990 b) Endocrinological responses to 5-HT1A Ann NY Acad Sci 600: 250–257
Frey PW, Colliver JA (1973) Sensitivity and response measures for discrimination learning. Learning Motivation 4: 327–342
Green AR, Goodwin GM (1987) The pharmacology of the hypothermic response of rodents to 8-OH-DPAT administration and the effects of psychotropic drugs on this response. In: Dourish CT, Hutson PH, Ahlenius S (eds) Brain 5-HT-1A receptors. Horwood, Chichester, pp 161–176
Hart RP, Clenda CC, Hamer RM (1991) Effects of buspirone and alprazolam on the cognitive performance of normal elderly subjects. Am J Psychiatry 148: 73–77
Koenig JI, Meltzer HY, Gudelsky GA (1988) 5-hydroxytryptamine1A receptor mediated effects of buspirone, gepirone and ipsaperone. Pharmacol Biochem Behav 29: 711–715
Krahling H, Fuchs A, Ruhland M, Schon U, Mol F, Tulp M (1988) KC-9172 (free base of KC-7218) — an antisychotic/anxiolytic compound. II. Discrimination from typical neuroleptics and benzodiazepine-like minor tranquilizers. Pharmacopsychiatry 21: 399–401
Krijzer F, Krahling H (1991) Umespirone. Antipsychotic anxiolyitic. Drugs Future 16: 437–442
Lesch K (1990) Corticotropin and cortisol secretion after central 5-HT1A receptor activation: effect of 5-HT receptor and beta-adrenoceptor antagonists. J Clin Endocrinol Metab 70: 670–674
Levy AD, Van de Kar LD (1992) Endocrine and receptor pharmacology of serotonergic anxiolytics, antipsychotics and antidepressants. Life Sci 51: 83–94
Matthews G, Jones DM, Chamberlain AG (1990) Refining the measurement of mood: The UWIST Mood Adjective Checklist. Br J Psychol 81: 17–42
Matussek N (1984) Drugs as tools for exploring neuroendocrine functions. In: Usdin E et al. (eds) Frontiers in biochemical and pharmcological research in depression: drugs as tools for exploring neuroendocrine functions. Raven Press, New York, pp 189–196
McClelland GR, Cooper SM, Pilgrim AJ (1990) A comparison of the central nervous system effects of haloperidol, chlorpromazine and sulpiride in normal volunteers. Br J Clin Pharmacol 30: 795–803
Meltzer HY, Flemming R, Robertson A (1983) The effect of buspirone on prolactin and growth hormone secretion in man. Arch Gen Psychiatry 40: 1099–1102
Meltzer HY, Flemming R (1982) Effect of buspirone on prolactin and growth hormone secretion in laboratory rodents and man. J Clin Psychiatry 43: 76–79
O'Hanlon JF (1991) Buspirone's effects on human performance and related variables. Eur Neuropsychopharmacol 1: 489–501
Obermair W, Breuel HP, Herrmann WM, Hadler D (1990) DN-2327, a novel anxiolytic. 17th Collegium Internationale Neuro-Psychopharmacologicum Congress, Kyoto
Rubin RT, Hays SE (1979) Variability of prolactin response to intravenous and intramuscular haloperidol in normal adult men. Psychopharmacology 61: 17–24
Ruhland M, Krahling H, Fuchs A, Schon U (1988) KC-9172 (free base of KC-7218) — an antipsychotic/anxiolytic compound. I. Antipsychotic and anxiolytic activity in comparison with chlorpromazine, clozapine, diazepam and buspirone. Pharmacopsychiatry 21: 396–398
Schaffler K, Klausnitzer W (1989) Placebo-controlled study on acute and subchronic effects of buspirone vs bromazepam utilizing psychomotor and cognitive assessments in healthy volunteers. Pharmacopsychiatry 22: 26–33
Spielberger CD (1983) Manual for the State-Trait Anxiety Inventory (Form Y). Consulting Psychologists, pp 79–92
Wesnes K, Simpson PM, Christmas L (1987) The assessment of human information processing abilities in psychpharmacology. In: Hindmarch I, Stonier PD (eds) Human psychopharmacology: measures and methods, vol 1. Wiley, Chichester Press, Palo Alto
Wiesel FA, Alfredsson G, Ehrnebo M, Sedvall G (1982) Prolactin response following intravenous and oral sulpiride in human subjects in relation to sulpiride concentrations. Psychopharmacology 76: 44–47
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Holland, R.L., Wesnes, K. & Dietrich, B. Single dose human pharmacology of umespirone. Eur J Clin Pharmacol 46, 461–468 (1994). https://doi.org/10.1007/BF00191912
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DOI: https://doi.org/10.1007/BF00191912