title: Serotonin receptor targeted therapy for migraine treatment: an overview of drugs in phase I and II clinical development.
abstract: Research has focused on serotonin (5-HT) 5-HT1Dand 5-HT1Freceptors to develop drugs acting through non-vasoconstrictive mechanisms for treating acute migraine and those targeting 5-HT2Band 5-HT7receptors for preventing migraine. Areas covered: This paper reviews antimigraine drugs targeting 5-HT receptors in one phase I trial (sumatriptan iontophoretic transdermal system, TDS) and five phase II clinical trials (PNU-142633, LY334370, lasmiditan, NOX-188). Expert opinion: Data from our overview on investigational drugs in phase I and II clinical trials using the 5-HT1B/1Dreceptor agonist (sumatriptan TDS), 5-HT1Dreceptor agonist (PNU-142633), 5-HT1Freceptor agonists (LY334370, lasmiditan) and a combined 5-HT1B/1Dreceptor agonist with nNOS inhibition (NOX-188) provided encouraging data for sumatriptan TDS and lasmiditan, disappointing results for PNU-142633, and promising findings for NOX-188. The 5-HT1Freceptor agonist lasmiditan, a drug acting through non-vasoconstrictive mechanisms, represents a promising safe, effective and tolerated acute migraine therapy also for patients at cardiovascular risk. Upcoming phase III trials should clarify the optimal lasmiditan dose and eventual clinical advantages over triptans. The negative results for the PNU-142633 trial prompt further studies using specific compounds more precisely targeting 5-HT1Dreceptors. Antagonism at 5-HT2Band 5-TH7receptors, a promising strategy to prevent migraine, is still limited to experimental migraine models.
authors.affiliation: a Headache and Pain Unit , IRCCS San Raffaele Pisana , Rome , Italy.
authors.forename: Piero
authors.initials: P
authors.lastname: Barbanti
authors.affiliation: a Headache and Pain Unit , IRCCS San Raffaele Pisana , Rome , Italy.
authors.forename: C
authors.initials: C
authors.lastname: Aurilia
authors.affiliation: a Headache and Pain Unit , IRCCS San Raffaele Pisana , Rome , Italy.
authors.forename: G
authors.initials: G
authors.lastname: Egeo
authors.affiliation: a Headache and Pain Unit , IRCCS San Raffaele Pisana , Rome , Italy.
authors.forename: L
authors.initials: L
authors.lastname: Fofi
authors.affiliation: b Department of Biomedical Sciences and Human Oncology , University of Bari 'Aldo Moro' , Bari , Italy.
authors.forename: R
authors.initials: R
authors.lastname: Palmirotta
mesh_terms: D000818:Animals; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D015195:Drug Design; D015507:Drugs, Investigational / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008881:Migraine Disorders / Q000188:drug therapy* / Q000503:physiopathology; D058990:Molecular Targeted Therapy; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D015507:Drugs, Investigational; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists
keywords: Lasmiditan; migraine; receptor; serotonin; treatment