Summary
In healthy man, MDL 73,005EF reduced body temperature and antagonised buspirone-induced increases in plasma ACTH and growth hormone. The effect on temperature is consistent with agonist activity at 5-HT 1A receptors, possibly located presynaptically on midbrain raphé neurones, whilst the effect on the hormone responses is consistent with antagonist activity at postsynaptic 5-HT1A receptors, possibly in the hypothalamus. The pharmacological profile of MDL 73,005EF in man differs from that of buspirone. MDL 73,005EF may have therapeutic advantages over buspirone and merits study in patients.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Anderson, I. M., Cowen, P. J., and Grahame-Smith, D. G. (1990). The effects of gepirone on neuroendocrine function and temperature in humans. Psychopharmacology 100: 498 – 503.
Cornfield, L. J., Nelson, D. L., Taylor, E. W., and Martin, A. R. (1989). MDL 73,005EF: partial agonist at the 5-HT,A receptor negatively linked to adenylate cyclase. Eur. J. Pharmacol. 173: 189–192.
Cowen, P. J., Anderson, I. M., and Grahame-Smith, D. G. (1990). Neuroendocrine effects of azapirones. J. Clin. Psychopharmacol. 10: 21S – 25S.
Gartside, S. E., Cowen, P. J., and Hjorth, S. (1990). Effects of MDL 73005EF on central pre-and postsynaptic 5-HT,A receptor function in the rat in vivo. Eur. J. Pharmacol. 191: 391–400.
Gilbert, F., Brazen, C., Tricklebank, M. D., and Stahl, S. M. (1988). Activation of the 5-HTIA receptor subtype increases rat plasma ACTH concentration. Eur. J. Pharmacol. 147: 431–439.
Gozlan, H., El Mestikawy, S., Pichat, L., Glowinski, J., and Hamon, M. (1983). Identification of presynaptic serotonin autoreceptors using a new ligand: 3H-PAT. Nature 305: 140–142.
Green, A. R., and Goodwin, G. M. (1987). The pharmacology of the hypothermic response of rodents to 8-OH-DPAT administration and the effects of psychotropic drug administration on this response. In: Dourish, C. T., Ahlenius, S., and Hutson P. H. (eds.), Brain 5-HT,A receptors. Chichester: Ellis Horwood, pp. 161–176.
Hibert, M. F., Mir, A. K., and Fozard, J. R. (1990). Serotonin (5-HT) receptors. In: Emmett J. C. (ed.), Comprehensive medicinal chemistry, The rational design, mechanistic study and therapeutic application of chemical compounds. Vol. 3, Membranes and receptors. Oxford: Pergamon Press, pp. 567–600.
Hibert, M., and Moser, P. (1990). MDL 72832 and MDL 73005EF: novel, potent and selective 5-HT,A receptor ligands with different pharmacological properties. Drugs of the future. 15: 159–170.
Jenkins, S. W., Donald, S., Robinson, M. D., Fabre, L. F., Andary, J. J., Messina, M. E., and Reich, L. A. (1990). Gepirone in the treatment of major depression. J. Clin. Psychopharmacol. 10: 77S - 85S.
Koenig, J. I., Meltzer, H. Y., and Gudelsky, G. A. (1988). 5-Hydroxytryptamine,A receptor-mediated effects of buspirone, gepirone and ipsapirone. Pharmacol. Biochem. Behay. 29: 711–715.
Lesch, K. P., Rupprecht, R., Poten, B., Müller, U., Söhnle, K., Fritze, J., and Schulte, H. M. (1989). Endocrine responses to 5-hydroxytryptamine1A receptor activation by ipsapirone in humans. Biol. Psychiatry 26: 203–205.
Lesch, K. P., Poten, B., Söhnle, K., and Schulte, H. M. (1990a). Pharmacology of the response to 5-HTIA receptor activation in humans. Eur. J. Clin. Pharmacol. 39: 17–19.
Lesch, K. P., Söhnle, K., Poten, B., Schoellnhammer, G., Rupprecht, R., and Schulte, H. M. (1990b). Corticotropin and cortisol secretion after central 5-hydroxytryptamine1A receptor activation: effects of 5-HT receptor and ß-adrenoceptor antagonists. J. Clin. Endocrinol. Metab. 70: 670–674.
Meller, E., Goldstein, M., and Bohmaker, K. (1990). Receptor reserve for 5-hydroxytryptamine IA-mediated inhibition of serotonin synthesis: possible relationship to anxiolytic properties of 5-hydroxytryptamine1A agonists. Mol. Pharmacol. 37: 231–237.
Meltzer, H. Y., Flemming, R., and Robertson, A. (1983). The effect of buspirone on prolactin and growth hormone secretion in man. Arch. Gen. Psychiatry 40: 1099–1102.
Middlemiss, D. N., and Fozard, J. R. (1983). 8-hydroxy-2-(di-n-propylamino)tetralin discriminates between subtypes of the 5-HT, recognition site. Eur. J. Pharmacol. 90: 151–153.
Moser, P. C. (1991). The effects of MDL 73005EF, ipsapirone, buspirone and (+) and (—)-MDL 72832A on 8-OH-DPAT-induced hypothermia in the rat and mouse (submitted for publication).
Moser, P. C., Tricklebank, M. D., Middlemiss, D. N., Mir, A. K., Hibert, M. F., and Fozard, J. R. (1990). Characterization of MDL 73005EF as a 5-HT,A selective ligand and its effects in animal models of anxiety: comparison with buspirone, 8-OH-DPAT and diazepam. Br. J. Pharmacol. 99: 343–349.
Newton, R. E., Marunycz, J. D., and Alderdice, M. T. (1986). Review of the side-effect profile of Buspirone. Amer. J. Med. 80: 17–21.
Sprouse, J. S., McCarty, D. R., and Dudley, M. W. (1990). Inhibition of dorsal raphé cell firing by MDL 73005EF: relationship to 5-HT,, receptor binding. Soc. Neurosci. Abstr. 16: 1034.
Traber, J., and Glaser, T. (1987). 5-HT,A receptor-related anxiolytics. Trends Pharmacol. Sci. 8: 432–437.
Van den Hooff, P., and Galvan, M. (1991). Electrophysiology of the 5-HT,A ligand MDL 73005EF in the rat hippocampal slice. Eur. J. Pharmacol. (in press).
Vergé, D., Duval, G., Patey, A., Gozlan, H., El Mestikawy, S., and Hamon, M. (1985). Presynaptic 5-HT autoreceptors on serotonergic cell bodies and/or dendrites but not terminals are of the 5-HT,A subtype. Eur. J. Pharmacol. 113: 463–464.
Yocca, F. D., Iben, L., and Meller, E. (1990). Lack of receptor reserve at postsynaptic 5-HT,A receptors linked to adenylyl cyclase in rat hippocampus. Soc. Neurosci. Abstr. 16: 1034.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1991 Birkhäuser Verlag Basel/Switzerland
About this chapter
Cite this chapter
Boyce, M.J., Hinze, C., Haegele, K.D., Green, D., Cowen, P.J. (1991). Initial Studies in Man to Characterise MDL 73,005EF, a Novel 5-HT1A Receptor Ligand and Putative Anxiolytic. In: Fozard, J.R., Saxena, P.R. (eds) Serotonin: Molecular Biology, Receptors and Functional Effects. Birkhäuser Basel. https://doi.org/10.1007/978-3-0348-7259-1_47
Download citation
DOI: https://doi.org/10.1007/978-3-0348-7259-1_47
Publisher Name: Birkhäuser Basel
Print ISBN: 978-3-0348-7261-4
Online ISBN: 978-3-0348-7259-1
eBook Packages: Springer Book Archive