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Pharmacological properties of a wide array of ergolines at functional alpha1-adrenoceptor subtypes

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Abstract

Ergot alkaloids act as (partial) agonists or antagonists at serotonergic, dopaminergic and α-adrenergic receptors. In contrast to their affinity at serotonergic (5-HT) and dopaminergic receptor subtypes, only limited information is available concerning their interaction with α-adrenoceptor subtypes. This especially holds true for native α-adrenoceptors. Therefore, we studied the pharmacological profile of 25 ergolines at α1A-, α1B- and α1D-adrenoceptors in vascular rings or strips of rat and guinea pig endowed with these receptors. Contractile responses were studied by measurement of isometric tension changes in rat tail artery (α1A, α1B), guinea pig spleen (α1B) and rat thoracic aorta (α1D). The anti-migraine drugs ergotamine and dihydroergotamine, the anti-parkinsonian drug lisuride and the anti-hyperprolactinemic drug terguride behaved as antagonists or low-efficacy partial agonists at all three α1-adrenoceptor subtypes with nanomolar receptor affinity. Derivatives of these drugs showed lower affinity at α1-adrenoceptors than the parent compounds. Each individual ergoline derivative tested showed low discriminatory capability at the subtypes, α1A, α1B, α1D. A low discriminatory power between the subtypes (α1A, α1B, α1D) seems to be a class effect of the ergolines. The nanomolar affinities of ergotamine, dihydroergotamine and lisuride for α1-adrenoceptors may affect their effectiveness as anti-migraine and anti-parkinsonian drugs, respectively.

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Acknowledgements

The study was supported in part by grants from Europäischer Fonds für regionale Entwicklung (EFRE, project no. 10021471) and EUREKA (project no. OE159) of the Ministry of Education, Youth and Sports of the Czech Republic.

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Author notes

  1. Sven Jähnichen

    Present address: The Leiden/Amsterdam Center for Drug Research, Department of Medicinal Chemistry, Vrije Universiteit Amsterdam, De Boelelaan 1083, 1081HV, Amsterdam, The Netherlands

Authors and Affiliations

  1. Institut für Pharmazie, Freie Universität Berlin, Königin-Luise-Str. 2+4, 14195, Berlin, Germany

    Tilo Görnemann, Sven Jähnichen & Heinz H. Pertz

  2. Axxonis Pharma AG, Schöneberger Str. 15, 10963, Berlin, Germany

    Björn Schurad, Klaus Peter Latté, Reinhard Horowski & Johannes Tack

  3. Alfarma s.r.o., Mokropeska 701, 25228, Cernosice, Czech Republic

    Miroslav Flieger

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  1. Tilo Görnemann
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  8. Heinz H. Pertz
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Correspondence to Heinz H. Pertz.

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Görnemann, T., Jähnichen, S., Schurad, B. et al. Pharmacological properties of a wide array of ergolines at functional alpha1-adrenoceptor subtypes. Naunyn-Schmied Arch Pharmacol 376, 321–330 (2008). https://doi.org/10.1007/s00210-007-0221-3

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  • DOI: https://doi.org/10.1007/s00210-007-0221-3

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