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Drug-target based cross-sectional analysis of olfactory drug effects

  • Pharmacoepidemiology and Prescription
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Background

Drug effects on the human sense of smell attract increasing interest, yet systematic evidence from controlled studies is sparse. The present cross-sectional approach to olfactory drug effects made use of the recent developments in informatics, knowledge discovery, and data mining allowing connecting drug-related information from humans with underlying molecular drug targets.

Methods

In this prospective cross-sectional study, n = 1008 outpatients at a general practitioner were enrolled. All currently taken medications were obtained, and olfactory function was assessed by means of a clinically established 12-item odor identification test. The association between the patients’ sense of smell and the administered medications was based (i) on the active pharmacological substances and (ii) on the molecular targets queried from the publicly accessible DrugBank database.

Results

Of the 168 different substances, six were taken sufficiently often to be analyzed. The administration of levothyroxine was associated with a higher olfactory score (p = 0.033). For the 168 drugs, 323 different targets could be queried. Thirty-one gene products were addressed sufficiently often to be analyzed. Besides agonistic targeting of thyroid hormone receptors (genes THRA1, THRB1) agreeing with the above result, antagonistically targeting the adrenoceptor alpha 1A (gene ADRA1A) by several unrelated medications was associated with a significantly higher olfactory score (p = 0.012).

Conclusions

The identified drug effects on olfaction are both biologically plausible based on supportive information from basic science studies. The novel molecular target-based approach suggested clear advantages over the classical drug or drug class-based approach. It increased the analyzable data volume fivefold and provided plausible hypotheses about mechanistic drug effects opening possibilities for drug discovery and repurposing.

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Funding

The research received funding from the “Landesoffensive zur Entwicklung wissenschaftlich-ökonomischer Exzellenz: LOEWE-Schwerpunkt: Anwendungsorientierte Arzneimittelforschung” (JL). The funders had no role in method design, data selection and analysis, decision to publish, or preparation of the manuscript.

Conflicts of interest

The authors have declared that no competing interests exist.

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Author notes

    Authors and Affiliations

    1. Institute of Clinical Pharmacology, Goethe-University, Theodor-Stern-Kai 7, 60590, Frankfurt am Main, Germany

      Jörn Lötsch

    2. Fraunhofer Project Group Translational Medicine and Pharmacology (IME-TMP), Theodor-Stern-Kai 7, 60590, Frankfurt am Main, Germany

      Jörn Lötsch

    3. Medic Center Nürnberg, Gibitzenhofstraße 150, 90443, Nürnberg, Germany

      Helena Daiker

    4. Smell and Taste Clinic, Department of Otorhinolaryngology, TU Dresden, Fetscherstrasse 74, 01307, Dresden, Germany

      Antje Hähner & Thomas Hummel

    5. Data Bionics Research Group, University of Marburg, Hans-Meerwein-Straße, 35032, Marburg, Germany

      Alfred Ultsch

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    1. Jörn Lötsch
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    Correspondence to Jörn Lötsch.

    Additional information

    Alfred Ultsch and Thomas Hummel contributed equally to this work.

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    Lötsch, J., Daiker, H., Hähner, A. et al. Drug-target based cross-sectional analysis of olfactory drug effects. Eur J Clin Pharmacol 71, 461–471 (2015). https://doi.org/10.1007/s00228-015-1814-2

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    • DOI: https://doi.org/10.1007/s00228-015-1814-2

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