title: Novel investigational therapeutics for panic disorder.
abstract: BACKGROUND
  Panic disorder (PD) is a common disabling anxiety disorder associated with relevant social costs. Effective anti-panic medications exist but have several drawbacks. From a clinical perspective, there is still a strong unmet need for more effective, faster acting and more tolerable therapeutic treatments.
  
  
  METHODS
  The authors review the available results on novel mechanism-based anti-panic drugs that are under investigation in animal studies up to Phase II studies. The preclinical studies investigated include: the modulators of the glutamate/orexin/cannabinoid systems, corticotrophin-releasing factor 1 (CRF1)/arginine vasopressine V₁B/angiotensin II receptor antagonists and neuropeptide S. The Phase I/II studies investigated include: the modulators of the glutamate system, isoxazoline derivative, translocator protein (18 kDa) ligands and CRF1/neurokinin receptor antagonists.
  
  
  CONCLUSIONS
  There has been little progress in recent times. However, glutamate- and orexin-related molecular targets may represent very promising opportunities for treating panic attacks. Very preliminary findings suggest that the antagonists of CRF1 and A-II receptors may have anti-panic properties. However, new medications for PD are far from being implemented in clinical use. The reasons are multiple, including: the heterogeneity of the disorder, the translational validity of animal models and the insufficient use of biomarkers in preclinical/clinical studies. Nevertheless, biomarker-based strategies, pharmacogenomics, 'personalized psychiatry' and the NIH's Research Domain Criteria approach could help to remove those obstacles limiting drug development.
authors.affiliation: Hermanas Hospitalarias - Villa San Benedetto Menni Hospital, Department of Clinical Neurosciences, FoRiPsi , via Roma 16, 22032, Albese con Cassano, Como , Italy +39031 4291511 ; +39031 427246 ; pernagp@gmail.com.
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Perna
authors.forename: Koen
authors.initials: K
authors.lastname: Schruers
authors.forename: Alessandra
authors.initials: A
authors.lastname: Alciati
authors.forename: Daniela
authors.initials: D
authors.lastname: Caldirola
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D015195:Drug Design; D015507:Drugs, Investigational / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D058990:Molecular Targeted Therapy; D016584:Panic Disorder / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D014151:Anti-Anxiety Agents; D015507:Drugs, Investigational
keywords: glutamate; novel drugs; orexin; panic disorder