Pharmacological implications of Bradykinins:
With such important roles in various physiological and pathological processes the role of Bradykinins and their receptors as drug targets is quite justifiable. The signalling of bradykinin receptors is mediated by kinins. Following ligand-binding, B1R and B2R signal through associated G proteins to activate signalling molecules like protein kinase C and phospholipases, and secondary messengers like inositol-1,4,5, -triphosphate, diacylglycerol, calcium, and arachidonic acid. These secondary messengers go on to modulate other signalling processes (e.g., nitric oxide or prostaglandin production).39 Following the discovery of bradykinin by Roche et al there are various research that has been undertaken to exploit its role in drug development. The invitro synthesis of BK peptide was introduced by solid phase preparation strategy by Merrifield.40 Since then, many kinin derivatives have been synthesized and investigated. These sequences include modifications (e.g., amino acid substitutions, reduction of amide bonds, N-terminal capping) that are aimed at conferring selectivity, stability to peptidases, agonist/antagonist properties and prolonging in vivo pharmacological effects.41 Icatibant, a B2R antagonist, is the only kinin to receive U.S. Food and Drugs Administration approval. It is indicated for the treatment of acute attacks of hereditary angioedema in adults with C1-esterase inhibitor deficiency.42Anatibant and fasitibant, B2R antagonists, advanced into clinical testing for treatment of traumatic brain injury and knee osteoarthritis, respectively. However, their development was discontinued due to the lack of efficacy.43,44 The hope is that new scaffolds will be able to find clinical utility in other disease setting
Table 1