Application of genomics to drug design: the example of the histamine H3 receptor - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue European Neuropsychopharmacology Année : 2001

Application of genomics to drug design: the example of the histamine H3 receptor

Jean-Charles Schwartz
  • Fonction : Auteur
  • PersonId : 1003648
Agnès Rouleau
  • Fonction : Auteur
Joël Tardivel-Lacombe
  • Fonction : Auteur
Florence Gbahou
  • Fonction : Auteur
Xavier Ligneau
  • Fonction : Auteur
Anne Héron
Astrid Sasse
  • Fonction : Auteur
Holger Stark
  • Fonction : Auteur
Walter Schunack
  • Fonction : Auteur
Robin Ganellin
  • Fonction : Auteur
Jean-Michel Arrang

Résumé

The histamine H3 receptor was characterized in the 1980s as an autoreceptor regulating histamine release in brain. Since then, selective drugs have been designed, many of them displaying a high potency in vivo, and used in many studies to delineate the implications of cerebral histaminergic systems in physiological functions such as arousal or cognitive functions. The recent cloning of the H3 receptor, more than 15 years later, has allowed to start molecular studies that led to important findings for optimization of drug design. In agreement some ligands display distinct affinities for the recombinant rat and human H3 receptors, a difference that we assign to two amino acids in the third transmembrane domain. In addition, H3 autoreceptors present in the brain display high constitutive activity including in vivo. As a consequence, inverse agonists enhance histamine neuron activity and constitute a novel potential therapeutic approach to schizophrenia and Alzheimer’s disease.

Dates et versions

hal-02129745 , version 1 (15-05-2019)

Identifiants

Citer

Jean-Charles Schwartz, Séverine Morisset, Agnès Rouleau, Joël Tardivel-Lacombe, Florence Gbahou, et al.. Application of genomics to drug design: the example of the histamine H3 receptor. European Neuropsychopharmacology, 2001, 11 (6), pp.441-448. ⟨10.1016/s0924-977x(01)00121-3⟩. ⟨hal-02129745⟩
30 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More