Targeting kinin receptors for the treatment of neurological diseases.
Kinins (bradykinin, kallidin and their active metabolites) are peptide autacoids with established functions in cardiovascular homeostasis, contraction and relaxation of smooth muscles, inflammation and nociception. They are believed to play a role in disease states like asthma, allergies, rheumatoid arthritis, cancer, diabetes, endotoxic and pancreatic shock, and to contribute to the therapeutic effects of ACE inhibitors in cardiovascular diseases. Although kinins are also neuromediators in the central nervous system, their involvement in neurological diseases has not been intensively investigated thus far. This review analyzes the potential of central kinin receptors as therapeutic targets for neurological disorders. Initial data highlight potential roles for B(1) receptor antagonists as antiepileptic agents, and for B(2) receptor antagonists (and/or B(1) agonists) in the treatment of stroke. Functional B(1) receptors located on T-lymphocytes and on the blood brain-barrier are also putative targets for the management of multiple sclerosis. However, successful elucidation of the therapeutic value of these new pharmacological approaches will require refinement of our knowledge on the physiology and cellular localization of central kinin receptors.
Rodi
D
D
Department of Clinical and Experimental Medicine, Section of Pharmacology, University of Ferrara, via Fossato di Mortara, 17-19, 44100 Ferrara, Italy.
Couture
R
R
Ongali
B
B
Simonato
M
M
D000818:Animals; D065168:Bradykinin Receptor Antagonists; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D009422:Nervous System Diseases / Q000188:drug therapy* / Q000378:metabolism; D018002:Receptors, Bradykinin / Q000819:agonists / Q000378:metabolism*
D065168:Bradykinin Receptor Antagonists; D018002:Receptors, Bradykinin