Abstract
Hydergine (co-dergocrine, ergoloid mesylates, dihydroergotoxine) is an ergot preparation shown to be of value in the treatment of senile mental impairment.
Inexperimental animals, Hydergine induces behaviors suggesting an influence on monoaminergic systems. Results from biochemical in vitro studies indicate that Hydergine has multiple effects and interacts directly with α-adrenoceptors, dopamine (DA), and serotonin (5-TH) receptor subtypes. In rat cortex slices, it blocks noradrenaline (NA)-induced cyclic adenosine monophosphate (cAMP) formation and facilitates evoked NA release. This indicates antagonistic effects at α 1 - and α 2 - adrenoceptors. Furthermore, Hydergine has mixed agonistic/antagonistic effects at postsynaptic DA receptors, stimulating adenylate cyclase and inhibiting action-potential-evoked acetylcholine release in the rat striatum. Also, at presynaptic DA receptors inhibiting evoked DA release in the rat striatum, Hydrergine has mixed agonistic/antagonistic effects.
Moreover, Hydergine was found to have mixed agonistic/antagonistic effects on 5-HT receptors involved in stimulating adenylate cyclase activity in homogenates of rat hippocampus. In slices of rat hippocampus, Hydergine enhanced electrically evoked acetylcholine release. Based on these findings, it is suggested that Hydergine can various transmitter systems in the central nervous system.
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
Adolfsson, R., Gottfries, C.G,. Roos, B.E., and Winblad, B.: Post-mortem distribution of dopamine and homovanillic acid in human brain, variations related to age, and a review of the literature. J. Neural Transm. 45, 81–105 (1979).
Anden, N.E., Carlsson, A., and Haggendal, J.: Adrenergic mechanisms. Ann. Rev. Pharmacol 9, 119–134 (1969).
Azmitia, E.C.: The serotonin-producing neurons of the midbrain median and dorsal raphe nuclei. In Handbook of Psychopharmacology, Vol. 9, pp. 233–314. New York, Plenum, 1978.
Beart, P.: Multiple dopamine receptors—new vistas. Trends in Pharmacol Sci. 5, 100–102 (1982).
Berthelsen, S., and Pettinger, W.A.: A functional basis for classification of a- adrenergic receptors. Life Sci. 21, 595–606 (1977).
Biirki, H.R., Asper, H., Ruch, W., and Ziiger, P.E.: Bromocriptine, dihydro-ergotoxine, methysergide, d-LSD, CF 25-397 and 29-712: Effects on the metabolism of the biogenic amines in the brain of the rat. Psychopharmacology 57, 221–237 (1978).
Carlsson, A.: Age-dependent changes in central dopaminergic and other mono- aminergic systems. Adv. Exp. Med. Bio. 113, 1–13 (1978).
Carlsson, A., Adolfson, R., Aquilonius, S.M., Gottfries, C.G., Orland, L., Svennerholm, L., and Winblad, B.: Biogenic amines in human brain in normal aging, senile dementia and chronic alcoholism. In Ergot Compounds and Brain Function: Neuroendocrine and Neuropsychiatric Aspects, pp. 295–304. New York: Raven, 1979.
Closse, A., Frick, W., Hauser, D., and Sauter, A.: Characterisation of 3H- bromocriptine binding to calf caudate membranes. In Psychopharmacology and Biochemistry of Neurotransmitter Receptors, pp. 463–474. New York: Elsevier/North Holland, 1980.
Cools, A.R., and Van Rossum, J.M.: Multiple receptors for brain dopamine in behavior regulation: Concept of dopamine-E and dopamine-J receptors. Life Sci. 27, 1237–1253 (1980).
Daly, J.W., Padgett, W., Creveling, C.R., Cantacuzene, D., and Kirch, K.L.: Cyclic AMP generating systems: Regional differences in activation by adrenergic receptors in rat brain. J. Neurosci. 1, 49–59 (1981).
Dravid, A.R.: Deficits in cholinergic enzymes and muscarinic receptors in the hippocampus and striatum of senescent rats. Effect of chronic Hydergine treatment. Arch. Int. Pharmacodyn. Ther. 264, 195–202 (1983).
Engel, G., Gothert, M., Miiller-Schweinitzer, E., Schlicker, E., Sistonen, L., and Stadler, P.A.: Evidence for common pharmacological properties of [3H]5- hydroxytryptamine binding sites, presynaptic 5-hydroxytryptamine autorecep- tors in CNS and inhibitor presynaptic 5-hydroxytryptamine receptors on sympathetic nerves. Naunyn-Schmiedebergs Arch. Pharmacol 324, 116–124 (1983).
Garau, L., Govani, S., Stefanini, E., Trabucchi, M., and Spano, P.F.: Dopamine receptors: Pharmacological and anatomical evidences indicate that two distinct dopamine receptor populations are present in rat striatum. Life Sci. 23, 1745–1750 (1978).
Goldstein, M., Lew, J.Y., Hata, F., and Lieberman, A.: Binding interactions of ergot alkaloids with monoaminergic receptors in the brain. Gerontology 24(Suppl. 1), 76–85 (1978).
Gottfries, C.G.: The metabolism of some neurotransmitters in aging and dementia disorders. Gerontology 28(Suppl. 2), 11–19 (1982).
Helmreich, J., Reimann, W., Hertting, G., and Starke, K.: Are presynaptic dopamine autoreceptors and postsynaptic dopamine receptors in the rabbit caudate nucleus pharmacologically different? Neuroscience 7, 1559–1566 (1982).
Jouvet, J.: The role of monoamines and acetylcholine containing neurons in the regulation of the sleep-waking cycle. Erg. Physiol. 64, 166–307 (1972).
Kebabian, J.W., and Calne, D.B.: Multiple receptors for dopamine. Nature 211, 93–96 (1979).
Loew, D., Vigouret, J.M., and Jaton, A.L.: Neuropharmacological investigations with two ergot alkaloids, Hydergine and bromocriptine. Postgrad. Med. J. 52(Suppl. 1), 40–46 (1976).
Loew, D.M., and Vigouret, J.M.: Neuropharmakologische Charakterisierung von Dihydroergotoxin (Hydergin). In Mutterkornalkaloide heute, pp. 69–79. Stuttgart: Georg Thieme, 1982.
Loew, D., and Weil, C.: Hydergine® in senile mental impairment. Gerontology 28, 54–74 (1982).
Markstein, R., and Wagner, H.: Effect of dihydroergotoxine on cyclic AMP generating systems in rat cerebral cortex slices. Gerontology 24(Suppl. 1), 94–105 (1978).
Markstein, R.: Dopamine receptor profile of Co-dergocrine (Hydergine®) and its components. European J. Pharmacol. 86, 145–155 (1983a).
Markstein, R.: Co-dergocrine has multiple effects on monoaminergic neuro-transmission. Fed. Proc. 42, 496 (1983b).
Markstein, R., Closse, A., and Frick, W.: Interaction of ergot alkaloids and their combination (Co-dergocrine) with a-adrenoceptors in the CNS. European J. Pharmacol. 93, 156–169 (1983).
McGeer, E.G., and McGeer, P.L.: Neurotransmitter metabolism in the aging brain. In Neurobiology of Aging, pp. 389–403. New York: Raven, 1976.
McGeer, E.G.: Neurotransmitter systems in aging and senile dementia. Progr. Neuro-Psychopharmacol. 5, 435–445 (1981).
Nieuwenhuys, R., Voogd, J., and Van Huijzen, Chr.: The Human Central Nervous System. Berlin: Springer-Verlag, 1978.
Olpe, H.R., and Steinmann, M.W.: The effect of vincamine, Hydergine and piracetom on the firing rate of Locus coeruleus neurons. Behav. Neural. Biol. 33, 249–251 (1982).
Peroutka, S.J., and Snyder, S.H.: Multiple serotonin receptors: Differential binding of [3H] serotonin, [3H]lysergic acid diethylamide and [3H] spiroperidol. Molec. Pharmacol 16, 687–699 (1979).
Peroutka, S.J., Lebowitz, R.M., and Snyder, S.H.: Two distinct central serotonin receptors with different physiological functions. Science 212, 827–829 (1979).
Pradhan, S.N.: Central neurotransmitter and aging. Life Sci. 26, 1643–1656 (1980).
Reader, T.A., Ferron, A., Descanies, L., and Jasper, H.H.: Modulatory role of biogenic amines in the cerebral cortex. Microiontophoretic studies. Brain Res. 160, 217–229 (1979).
Schild, H.O.: pA and competitive drug antagonism. Br. J. Pharmacol 4, 277–280 (1949).
Starke, K.: Regulation of noradrenaline release by presynaptic receptor systems. Rev. Physiol Biochem. Pharmacol 77, 1–124 (1977).
Starke, K., Reimann, W., Zumstein, A., and Hertting, G.: Effect of dopamine agonists and antagonists on release of dopamine in the rabbit caudate nucleus in vitro. Naunyn-Schmiedebergs Arch. Pharmacol 305, 27–36 (1978).
Stoof, J.C., Thieme, R.E., Vrijmoed-De Vries, M.C., and Mulder, A.H.: In vitro acetylcholine release from rat caudate nucleus as a new model for testing drugs with dopamine receptor activity. Naunyn-Schmiedebergs Arch. Pharmacol 309, 119–124 (1979).
U’Prichard, D.C., Greenberg, D.A., and Snyder, S.H.: Binding characteristics of a radiolabeled agonist and antagonist at central nervous system. Alpha- noradrenergic receptors. Mol. Pharmacol 21, 454–473 (1977).
Venn, R.D.: Clinical pharmacology of ergot alkaloids in senile cerebral insuf-ficiency. In Ergot Alkaloids and Related Compounds, pp. 533–566. New York: Springer-Verlag, 1978.
Vigouret, J.M., Biirki, H.R., Jaton, A.L., Ziiger, P.E., and Loew, D.M.: Neuro-chemical and neuropharmacological investigations with four ergot derivatives: Bromocriptine, dihydroergotoxine, CF 25-397 and CM 29-712. Pharmacology 16(Suppl. 1), 156–173 (1978).
Vigouret, J.M., Jaton, A.L., and Loew, D.: Increased sensitivity after repeated administration of ergot derivatives in rats. Experientia 35, 953 (1979).
Woodward, C., Moises, H.C., Waterhouse, P.D., Hoffer, B., and Freedman, R.: Modulatory actions of norepinephrine in the central nervous system. Fed. Proc. 38, 2109–2116 (1979).
Züer, P.E., Vigouret, J.M., and Loew, D.M.: Inhibition of reserpine-induced PGO-waves in the cat by ergot derivatives. Experientia 34, 637–639 (1978).
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1985 Springer-Verlag New York Inc.
About this paper
Cite this paper
Markstein, R. (1985). Hydergine: Interaction with Neurotransmitter Systems in the Central Nervous System. In: Gaitz, C.M., Samorajski, T. (eds) Aging 2000: Our Health Care Destiny. Springer, New York, NY. https://doi.org/10.1007/978-1-4612-5058-6_30
Download citation
DOI: https://doi.org/10.1007/978-1-4612-5058-6_30
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-4612-9544-0
Online ISBN: 978-1-4612-5058-6
eBook Packages: Springer Book Archive