Skip to main content
SpringerLink
Log in

Typical and atypical neuroleptics are potent antagonists at α1-adrenoceptors of the dorsal lateral geniculate nucleus

An electrophysiological study

  • Published:
Naunyn-Schmiedeberg's Archives of Pharmacology Aims and scope Submit manuscript

Summary

The present electrophysiological studies examined the actions of neuroleptics at central α1adrenoceptors in the rat. In single-cell recording experiments, typical and atypical neuroleptics, when administered systemically or locally (iontophoresis and pressure ejection), were found to be potent antagonists of activating α1adrenoceptor responses in the dorsal lateral geniculate nucleus (dLGN). Doses of neuroleptics effective as antagonists at α1adrenoceptors had very weak effects as muscarinic receptors in the dLGN. Since doses of neuroleptics employed in the present study were within the clinical range, it appears likely that central α1adrenoceptors would be blocked during neuroleptic therapy in humans.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Anden NE, Butcher GS, Corrodi H, Fuxe K, Ungerstedt U (1970) Receptor activity and turnover of dopamine and noradrenaline after neuroleptics. Eur J Pharmacol 11:303–314

    Google Scholar 

  • Angst J, Bente D, Berner P, Heimann H, Helmchen H, Hippius H (1971) Das klinische Wirkungsbild von Clozapin. Pharmakopsychiatry 4:201–211

    Google Scholar 

  • Bernheimer H, Birkmayer W, Hornykiewicz O, Jellinger K, Seitelberger F (1973) Brain dopamine and the syndromes of Parkinson and Huntington. J Neurol Sci 20:415–428

    Google Scholar 

  • Blumberg JB, Vetulani J, Stawarz,RJ, Sulser F (1976) The noradrenergic cyclic AMP generating system in the limbic forebrain: Pharmacological characterization and possible role in the mode of action of antipsychotics. Eur J Pharmacol 37:357–366

    Google Scholar 

  • Bradshaw CM, Pun RYK, Slater NT, Stooker MJ, Szabadi E (1980) Comparison of the effect of haloperidol on excitatory responses of cortical neurones to dopamine, noradrenaline and phenylephrine. Br J Pharmacol 71:243p-244p

    Google Scholar 

  • Bunney BS, Aghajanian GK (1974) Antipsychotic drugs and central dopaminergic neurons: a model for predicting therapeutic efficacy and incidence of extrapyramidal side effects. In: Sudilovsky A, Gershon S, Beer B (eds) Predictiveness in psychopharmacology. Raven Press, New York

    Google Scholar 

  • Bunney BS, Aghajanian GK (1975) The effect of antipsychotic drugs on the firing of dopaminergic neurons: A reappraisal. In: Sedvall G (ed) Antipsychotic drugs, pharmacodynamics and pharmacokinetics. Pergamon Press, New York, pp 305–318

    Google Scholar 

  • Burki HR, Ruch W, Asper H (1975) Effects of clozapine, thioridazine, perlapine and haloperidol on the metabolism of the biogenic amines in the brain of the rat. Psychopharmacologica 41:27–33

    Google Scholar 

  • Carlsson A, Lindqvist M (1963) Effect of chlorpromazine or haloperidol on formation of 3-methoxytyramine and normetanephrine in mouse brain. Acta Pharmacol et Toxicol 20:140–144

    Google Scholar 

  • Clough DP, Hatton R (1981) Hypotensive and sedative effects of α-adrenoceptor agonists: relationship to α1- and α1adrenoceptor potency. Br J Pharmacol 73:595–604

    Google Scholar 

  • DeJonge A, VanMeel JCA, Timmermans PBMWM, VanZwieten PA (1981) A lipophilic, selective α1adrenoceptor agonist: 2-(2-chloro-5-trifluoromethylphenylimino) imidazolidine (ST 587). Life Sci 28:2009–2016

    Google Scholar 

  • Fuxe K (1975) Evidence for the existence of monoamine neurons in the central nervous system: I. V. The distribution of monoamine terminals in the central nervous system. Acta Physiol Scand 64: Suppl 247:39–85

    Google Scholar 

  • Greenblatt EN, Coupet J, Rauch E, Szues-Myers VA (1980) IS dopamine antagonism a requisite of neuroleptic activity. Arch Int Pharmacodyn Ther 248:105–119

    Google Scholar 

  • Greengrass P, Bremmer R (1979) Binding characteristics of3H-prazosin to rat brain α-adrenergic receptors. Eur J Pharmacol 55:323–326

    Google Scholar 

  • Haigler HJ, Aghajanian GK (1974) Lysergic acid diethylamide and serotonin: a comparison of effects on serotonergic neurons and neurons receiving a serotonergic input. J Pharmacol Exp Ther 188:688–699

    Google Scholar 

  • Huchet AM, Chelly J, Schmitt H (1981) Role of α1- and α1adrenoceptors in the modulation of the baroreflex vagal bradycardia. Eur J Pharmacol 71:455–461

    Google Scholar 

  • Iversen LL (1975) Dopamine receptors in the brain. Science 188:1084–1089

    Google Scholar 

  • Jenner P, Marsden CD (1979) The substituted benzamides: a novel class of dopamine antagonists. Life Sci 25:479–486

    Google Scholar 

  • Jones BE, Moore RY (1977) Ascending projections of the locus coeruleus in the rat. II. Autoradiographic study. Brain Res 127:23–53

    Google Scholar 

  • Kafka MS, VanKamen DP, Kleinman JE, Nürnberger JI, Siever LJ, Unde TW, Polinsky RJ (1980) Alpha-adrenergic receptor function in schizophrenia, affective disorders and some neurological diseases. Commun Psychopharmacol 4:477–486

    Google Scholar 

  • Kessler KA, Waltezky JP (1981) Clinical use of the antipsychotics. Am J Psychiat 138:202–209

    Google Scholar 

  • Kety SS, Matthysse S (1972) Prospects for research on schizophrenia; a report based on an NRP work session. Neurosci Res Prog Bull 10:370–507

    Google Scholar 

  • Laduron P (1980) Dopamine receptor: from an in vivo concept towards a molecular characterization. Trends Pharmacol Sci Dec:471–474

  • Laduron PM, Leysen JE (1978) Is the low incidence of extrapyramidal side-effects of antipsychotics associated with antimuscarinic properties. J Pharm Pharmacol 30:120–122

    Google Scholar 

  • Langer G, Sachar EJ, Gruen PH, Halpern FS (1977) Human prolactin responses to neuroleptic drugs correlate with antischizophrenic potency. Nature 266:639–640

    Google Scholar 

  • Leysen JE, Niemeqeers CJE, Tollenaere JP, Laduron PM (1978) Serotonergic component of neuroleptic receptors. Nature 272:168–171

    Google Scholar 

  • Nishiura M (1976) Clinico-pharmacological studies of sulpiride. Curr Ther Res 20:164–172

    Google Scholar 

  • Peroutka SJ, U'Prichard DC, Greenberg DA, Snyder SH (1977) Neuroleptic drug interactions with norepinephrine alpha receptor binding sites in rat brain. Neuropharmacology 16:549–556

    Google Scholar 

  • Peroutka SJ, Snyder SH (1980) Relationship of neuroleptic drug effects at brain dopamine, serotonin, α-adrenergic and histamine receptors to clinical potency. Am J Psychiat 137:1517–1522

    Google Scholar 

  • Randrup A, Munkvad I (1972) Influence of amphetamine on animal behavior stereotypy functional impairment and possible animal human correlations. Psychiat Neurol Neurochem 75:193–292

    Google Scholar 

  • Robinson SE, Sulser F (1976) The noradrenergic cyclic AMP generating system in the rat limbic forebrain and its stereospecificity for butaclamol. J Pharm Pharmacol 28:645–646

    Google Scholar 

  • Robinson SE, Berney S, Mishra R, Sulser F (1979) The relative role of dopamine and norepinephrine receptor blockade in the action of antipsychotic drugs: metoclopramide, thiethylperazine and molindone as pharmacological tools. Psychopharmacology 64:141–147

    Google Scholar 

  • Rogawski MA, Aghajanian GK (1980) Activation of lateral geniculate-neurons by norepinephrine: mediation by an α-adrenergic receptor. Brain Res 182:345–359

    Google Scholar 

  • Snyder S, Greenberg D, Yamamura HI (1974) Antischizophrenic drugs and brain cholinergic receptors. Arch Gen Psychiat 31:58–61

    Google Scholar 

  • Stille G, Lauener H, Eichenberger E (1971) The pharmacology of 8-chloro-11-(4-methyl-1-piperazinyl)-SH-dibenzo (6,C) (1,4) diazepine (clozapine). IC Farmaco 26:603–625

    Google Scholar 

  • Stille G, Sayers AC, Lauener H, Eichenberger E (1973) 6-(4-methyl-1-piperazinyl)-morphanthridine (perlapine), a new tricyclic compound with sedative and sleep promoting properties. Psychopharmacologia (Berl) 28:325–337

    Google Scholar 

  • Timmermans PBMWM, VanZwieten PA (1981) The postsynaptic α1adrenoceptor. J Auton Pharmacol 1:171–183

    Google Scholar 

  • Wang RY, Aghajanian GK (1977) Inhibition of neurons in the amygdala by dorsal raphe stimulation: mediation through a direct serotonergic pathway. Brain Res 120:85–102

    Google Scholar 

  • VanPraag HM, Korf J, Dols LCW (1976) Clozapine versus perphenazine the value of the biochemical mode of action of neuroleptics in predicting their therapeutic activity. Br J Psychiat 129:547–555

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Departments of Psychiatry and Pharmacology, Yale University School of Medicine, 34 Park Street, 06508, New Haven, CT, USA

    Jwaharlal Marwaha & George K. Aghajanian

  2. Connecticut Mental Health Center, 34 Park Street, 06508, New Haven, CT, USA

    Jwaharlal Marwaha & George K. Aghajanian

Authors
  1. Jwaharlal Marwaha
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. George K. Aghajanian
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Marwaha, J., Aghajanian, G.K. Typical and atypical neuroleptics are potent antagonists at α1-adrenoceptors of the dorsal lateral geniculate nucleus. Naunyn-Schmiedeberg's Arch. Pharmacol. 321, 32–37 (1982). https://doi.org/10.1007/BF00586345

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00586345

Key words

Search

Navigation