163554-55-0Relevant articles and documents
Selective cathepsin s inhibition with MIV-247 attenuates mechanical allodynia and enhances the antiallodynic effects of gabapentin and pregabalin in a mouse model of neuropathic pain
Hewitt, Ellen,Pitcher, Thomas,Rizoska, Biljana,Tunblad, Karin,Henderson, Ian,Sahlberg, Britt-Louise,Grabowska, Urszula,Classon, Bj?rn,Edenius, Charlotte,Malcangio, Marzia,Lindstr?m, Erik
, p. 387 - 396 (2016)
Cathepsin S inhibitors attenuate mechanical allodynia in preclinical neuropathic pain models. The current study evaluated the effects when combining the selective cathepsin S inhibitor MIV-247 with gabapentin or pregabalin in a mouse model of neuropathic pain. Mice were rendered neuropathic by partial sciatic nerve ligation. MIV-247, gabapentin, or pregabalin were administered alone or in combination via oral gavage. Mechanical allodynia was assessed using von Frey hairs. Neurobehavioral side effects were evaluated by assessing beamwalking. MIV-247, gabapentin, and pregabalin concentrations in various tissueswere measured. Oral administration of MIV-247 (100-200 μmol/kg) dose-dependently attenuated mechanical allodynia by up to approximately 50%reversal when given as a single dose or when given twice daily for 5 days. No behavioral deficits were observed at any dose of MIV-247 tested. Gabapentin (58-350 μmol/kg) and pregabalin (63-377 μmol/kg) also inhibited mechanical allodynia with virtually complete reversal at the highest doses tested. The minimum effective dose of MIV-247 (100 μmol/kg) in combination with the minimum effective dose of pregabalin (75 μmol/kg) or gabapentin (146 μmol/kg) resulted in enhanced antiallodynic efficacy without augmenting side effects. A subeffective dose of MIV-247 (50 μmol/kg) in combination with a subeffective dose of pregabalin (38 μmol/kg) or gabapentin (73 μmol/kg) also resulted in substantial efficacy. Plasma levels of MIV-247, gabapentin, and pregabalin were similar when given in combination as to when given alone. Cathepsin S inhibition with MIV-247 exerts significant antiallodynic efficacy alone, and also enhances the effect of gabapentin and pregabalin without increasing side effects or inducing pharmacokinetic interactions.
CYSTEINE PROTEASE INHIBITORS
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, (2011/06/26)
Compounds of the formula (I) wherein R1a is H; and R1b is C1-C6alkyl, Carbocyclyl or Het; or R1a and R1b together define a saturated cyclic amine with 3-6 ring atoms; R2a and Rs
NEW CATHEPSIN S PROTEASE INHIBITORS, USEFUL IN THE TREATMENT OF E.G. AUTOIMMUNE DISORDERS, ALLERGY AND CHRONIC PAIN CONDITIONS
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, (2012/01/06)
Compounds of the formula (I) wherein R2a and R2b are independently H, halo, C1-C4alkyl, C1-C4haloalkyl or C1-C4alkoxy, or R2a and R2b together wi