title: Drug-target based cross-sectional analysis of olfactory drug effects.
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.
authors: Institute of Clinical Pharmacology, Goethe-University, Theodor-Stern-Kai 7, 60590, Frankfurt am Main, Germany, j.loetsch@em.uni-frankfurt.de.
authors: Jörn
authors: J
authors: Lötsch
authors: Helena
authors: H
authors: Daiker
authors: Antje
authors: A
authors: Hähner
authors: Alfred
authors: A
authors: Ultsch
authors: Thomas
authors: T
authors: Hummel
mesh_terms: D000293:Adolescent; D058646:Adrenergic alpha-1 Receptor Agonists / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003430:Cross-Sectional Studies; D016503:Drug Delivery Systems / Q000379:methods; D055808:Drug Discovery / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009812:Odorants / Q000032:analysis*; D011446:Prospective Studies; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism; D011988:Receptors, Thyroid Hormone / Q000378:metabolism; D012903:Smell / Q000187:drug effects*; D013974:Thyroxine / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D058646:Adrenergic alpha-1 Receptor Agonists; D018340:Receptors, Adrenergic, alpha-1; D011988:Receptors, Thyroid Hormone; D013974:Thyroxine