Non-antibacterial tetracycline formulations: clinical applications in dentistry and medicine

摘要

In1983,itwasfirstreportedthattetracyclines(TCs)canmodulatethehostresponse,including(butnotlimitedto)inhibitionofpathologicmatrixmetalloproteinase(MMP)activity,andbymechanismsunrelatedtotheantibacterialpropertiesofthesedrugs.Soonthereafter,strategiesweredevelopedtogeneratenonantibacterialformulations(subantimicrobial-dosedoxycycline;SDD)andcompositions(chemicallymodifiedtetracyclines;CMTs)ofTCsashost-modulatingdrugstotreatperiodontalandotherinflammatorydiseases.Thisreviewfocusesonthehistoryandrationaleforthedevelopmentof:(a)SDDwhichledtotwogovernment-approvedmedications,oneforperiodontitisandtheotherforacne/rosaceaand(b)CMTs,whichledtotheidentificationoftheactivesiteofthedrugsresponsibleforMMPinhibitionandtostudiesdemonstratingevidenceofefficacyofthemostpotentofthese,CMT-3,asananti-angiogenesisagentinpatientswiththecancer,Kaposi’ssarcoma,andasapotentialtreatmentforafatallungdisease(acuterespiratorydistresssyndrome;ARDS).Inaddition,thisreviewdiscussesanumberofclinicalstudies,someupto2years’duration,demonstratingevidenceofsafetyandefficacyofSDDformulationsinhumanswithoralinflammatorydiseases(periodontitis,pemphigoid)aswellasmedicaldiseases,includingrheumatoidarthritis,post-menopausalosteopenia,typeIIdiabetes,cardiovasculardiseases,andarareandfatallungdisease,lymphangioleiomyomatosis.Keywords:tetracyclines;host-modulation;matrixmetalloproteinaseinhibitors;clinicalapplications(Published:12October2012)Citation:JournalofOralMicrobiology2012,4:19227-http://dx.doi.org/10.3402/jom.v4i0.19227