Skip to main content
SpringerLink
Log in

An analysis of the effects of amezinium on postganglionic sympathetic neurones

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

Summary

Effects of amezinium on postganglionic sympathetic neurones were studied in the heart and pulmonary artery of the rabbit.

  1. 1.

    In isolated perfused hearts, amezinium increased the rate of beat. The effect was antagonized by propranolol or cocaine and by pretreatment with reserpine or 6-hydroxydopamine.

  2. 2.

    In hearts pre-perfused with 3H-noradrenaline, amezinium 0.003 μM reduced the outflow of 3H-DOPEG by 50%. 0.1 μM and higher concentrations in addition reduced the outflow of 3H-MOPEG and increased the outflow of 3H-noradrenaline and 3H-NMN. The outflow of 3H-DOMA and 3H-VMA was not changed. Cocaine prevented the effects of amezinium. When hearts were first perfused with amezinium and then with 3H-noradrenaline, the subsequent outflow of 3H-DOMA was abolished.

  3. 3.

    Hearts were perfused with 3H-noradrenaline 50 nM, and the arterio-venous difference of the 3H-amine was determined. Amezinium 0.29 μM reduced the arterio-venous difference by 50%.

  4. 4.

    Rabbits received intravenous injections of amezinium and were killed 30 min later. The hearts were perfused with 3H-noradrenaline. Pretreatment with amezinium 10 μg/kg diminished the outflow of 3H-DOPEG during the perfusion with 3H-noradrenaline, whereas pretreatment with 1 mg/kg was necessary to decrease the arterio-venous difference of 3H-noradrenaline.

  5. 5.

    Amezinium 4 μM caused 50% inhibition of MAO in crude homogenates and mitochondrial preparations from rabbit hearts, with 3H-noradrenaline as substrate.

  6. 6.

    In pulmonary artery strips preincubated with 3H-noradrenaline, the effects of amezinium on the outflow of 3H-compounds were similar to its effects in the heart. In addition, amezinium reduced the overflow of 3H-DOPEG and enhanced contractions elicited by electrical stimulation.

  7. 7.

    Amezinium is a relatively weak inhibitor of MAO in cell-free preparations. However, in the intact tissue it is a very potent inhibitor of the MAO inside noradrenergic neurones because it is concentrated in these neurones by the noradrenaline uptake mechanism. Being a substrate of uptake, amezinium also inhibits the uptake of noradrenaline. In contrast to bretylium which also inhibits intraneuronal MAO, amezinium is not an adrenergic neurone blocking agent. Concentrations higher than those needed to block intraneuronal MAO in addition release noradrenaline and thereby increase the rate of cardiac contraction.

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

Abbreviations

DOMA:

3,4-dihydroxymandelic acid

DOPEG:

3,4-dihydroxyphenylglycol

MAO:

monoamine oxidase (EC 1.4.3.4.)

MOPEG:

3-methoxy-4-hydroxyphenylglycol

NA:

noradrenaline

NMN:

normetanephrine

OMDA:

O-methylated deaminated metabolites, i. e., sum of MOPEG and VMA

VMA:

3-methoxy-4-hydroxymandelic acid

References

  • Adler-Graschinsky E, Langer SZ, Rubio MC (1972) Metabolism of norepinephrine released by phenoxybenzamine in isolated guinea-pig atria. J Pharmacol Exp Ther 180: 286–301

    Google Scholar 

  • Endo T, Starke K, Bangerter A, Taube HD (1977) Presynaptic receptor systems on the noradrenergic neurones of the rabbit pulmonary artery. Naunyn-Schmiedeberg's Arch Pharmacol 296: 229–247

    Google Scholar 

  • Erwin VG (1973) Oxidative-reductive pathways for metabolism of biogenic aldehydes. In: Usdin E, Snyder SH (eds) Frontiers in Catecholamine Research. New York, Pergamon Press, p 161

    Google Scholar 

  • Fiebig ER, Trendelenburg U (1978) The neuronal and extraneuronal uptake and metabolism of 3H-(−)-noradrenaline in the perfused rat heart. Naunyn-Schmiedeberg's Arch Pharmacol 303: 21–35

    Google Scholar 

  • Furchgott RF, Garcia PS, Wakade AR, Cervoni P (1971) Interactions of bretylium and other drugs on guinea-pig atria: Evidence for inhibition of neuronal monoamine oxidase by bretylium. J Pharmacol Exp Ther 179: 171–185

    Google Scholar 

  • Graefe KH, Stefano FJE, Langer SZ (1973) Preferential metabolism of (−)-3H-norepinephrine through the deaminated glycol in the rat vas deferens. Biochem Pharmacol 22: 1147–1160

    Google Scholar 

  • Graefe KH, Bönisch H, Fiebig R, Trendelenburg U (1975) Extraneuronal uptake and metabolism of catecholamines in isolated perfused hearts. In: Ahtee L (ed) Proceedings of the Sixth International Congress of Pharmacology, vol 2, Helsinki, p 117

  • Graefe KH, Bönisch H, Keller B (1978) Saturation kinetics of the adrenergic neurone uptake system in the perfused rabbit heart. A new method for determination of initial rates of amine uptake. Naunyn-Schmiedeberg's Arch Pharmacol 302: 263–273

    Google Scholar 

  • Horita A (1968) The influence of age on the recovery of cardiac monoamine oxidase after irreversible inhibition. Biochem Pharmacol 17: 2091–2096

    Google Scholar 

  • Keller R, Oke A, Mefford I, Adams RN (1976) Liquid chromatographic analysis of catecholamines — routine assay for regional brain mapping. Life Sci 19: 995–1004

    Google Scholar 

  • Langer SZ (1974) Selective metabolic pathways for noradrenaline in the peripheral and in the central nervous system. Med Biol 52: 372–383

    Google Scholar 

  • Lehmann HD, Schuster J, Giertz H (1979) Haemodynamic effects of a new sympathomimetic: Amezinium metilsulfate (LU 1631). Naunyn-Schmiedeberg's Arch Pharmacol 308: R16

    Google Scholar 

  • Lenke D, Gries J, Kretzschmar R (1979) Pharmacological studies on the mechanism of action on amezinium metilsulfate (LU 1631), a new compound with sympathomimetic action. Naunyn-Schmiedeberg's Arch Pharmacol 308: R12

    Google Scholar 

  • Lindmar R, Muscholl E (1961) Die Wirkung von Cocain, Guanethidin, Reserpin, Hexamethonium, Tetracain und Psicain auf die Noradrenalin-Freisetzung aus dem Herzen. Naunyn-Schmiedeberg's Arch exp Pathol Pharmakol 242: 214–227

    Google Scholar 

  • Lindmar R, Muscholl E (1964) Die Wirkung von Pharmaka auf die Elimination von Noradrenalin aus der Perfusionsflüssigkeit und die Noradrenalinaufnahme in das isolierte Herz. Naunyn-Schmiedeberg's Arch exp Pathol Pharmakol 247: 469–492

    Google Scholar 

  • Mack F, Bönisch H (1979) Dissociation constants and lipophilicity of catecholamines and related compounds. Naunyn-Schmiedeberg's Arch Pharmacol 310: 1–9

    Google Scholar 

  • Maxwell RA, White HL (1978) Tricyclic and monoamine oxidase inhibitor antidepressants: Structure-activity relationships. In: Iversen LL, Iversen SD, Snyder SH (eds) Handbook of Psychopharmacology vol 14. New York, Plenum Press, p 83

    Google Scholar 

  • Pettinger AW, Korn A, Spiegel H, Solomon HM, Porcelinko R, Abrams WB (1969) Debrisoquine, a selective inhibitor of intraneuronal monoamine oxidase in man. J Clin Pharmacol 10: 667–674

    Google Scholar 

  • Starke K (1978) Introduction. In: Azevedo I, Guimaraes S, Moura D, Paiva MQ (eds) Proceedings of the 3rd Meeting on Adrenergic Mechanisms, Porto, p 61

  • Starke K, Steppeler A, Zumstein A, Henseling M, Trendelenburg U (1980) False labelling of commercially available 3H-catecholamines? Naunyn-Schmiedeberg's Arch Pharmacol 311: 109–112

    Google Scholar 

  • Steppeler A (1980) Selective inhibition of intraneuronal MAO by amezinium. Naunyn-Schmiedeberg's Arch Pharmacol 311: R61

    Google Scholar 

  • Steppeler A, Pfändler R (1979) A neurochemical study of amezinium. Naunyn-Schmiedeberg's Arch Pharmacol 308: R13

    Google Scholar 

  • Traut M (1979) Inhibition of noradrenaline uptake and of monoamine oxidase by ameziniummetilsulfat (LU 1631). Naunyn-Schmiedeberg's Arch Pharmacol 308: R12

    Google Scholar 

  • Trendelenburg U, Bönisch H, Graefe KH, Henseling M (in press) The rate constants for the efflux of metabolites of catecholamines and phenylethylamines. Pharmacol Rev 31

  • Weitzell R, Tanaka T, Starke K (1979) Pre- and postsynaptic effects of yohimbine stereoisomers on noradrenergic transmission in the pulmonary artery of the rabbit. Naunyn-Schmiedeberg's Arch Pharmacol 308: 127–136

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Pharmakologisches Institut, Universität Freiburg, Hermann-Herder-Straße 5, D-7800, Freiburg i. B., Federal Republic of Germany

    A. Steppeler, R. Pfändler, L. Hedler & K. Starke

Authors
  1. A. Steppeler
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R. Pfändler
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. L. Hedler
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. K. Starke
    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

Steppeler, A., Pfändler, R., Hedler, L. et al. An analysis of the effects of amezinium on postganglionic sympathetic neurones. Naunyn-Schmiedeberg's Arch. Pharmacol. 314, 1–11 (1980). https://doi.org/10.1007/BF00498425

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00498425

Key words

Search

Navigation