Pregabalinisanon-gamma-aminobutyricacid(GABA)receptoragonistorantagonist.Itisanewcalciumchannelmodulatorthatcanblockvoltage-dependentcalciumchannelsandreducethereleaseofneurotransmitters.Clinically,itismainlyusedforneuralgiarelatedtodiabeticperipheralneuropathy,post-herpeticneuralgiaandadjuvanttreatmentofadultpartialepilepsy,generalizedanxietydisorder,centralneuralgia(includingspinalcordinjury,strokeandneuralgiaassociatedwithmultiplesclerosis)andFibromyalgia.R&DprocessPregabalinisananalogoftheneurotransmittergamma-aminobutyricacid(GABA),soldunderthetradenameLyrica.InDecember2004,theFDAapprovedpregabalinasadrugforthetreatmentofdiabeticneuralgiaandherpeszosterneuralgia.PregabalinisthefirstdrugapprovedintheUnitedStatesandEuropeforthetreatmentofbothtypesofpain.InJune2005,pregabalinwasapprovedasanadjuvanttreatmentforpartial-onsetepilepsyinadults.InMarch2006,theEuropeanUnionapprovedpregabalinforthetreatmentofgeneralizedanxietydisorder(GAD)andsocialanxietydisorder(SAD).IndicationsPregabalinismainlyusedforthetreatmentofperipheralneuralgiaandadjuvanttreatmentoflocalizedpartialepilepsy.PharmacologicaleffectsPregabalinhasagoodtherapeuticeffectonepilepsy.Studiesonvariousanimalepilepticseizuremodelshaveshownthatpregabalincansignificantlypreventepilepticseizures,anditsactivedoseis3-10timeslowerthangabapentin.Studieshavefoundthatpregabalincanreducethesensoryandmotorspinalreflexesstimulatedbypinchingthetipofthetoeinrats,reducebehaviorsrelatedtodiabetes,peripheralnerveinjury,orchemicallytreatedneuropathicanimalpainmodels,andinhibitorreducepain-relatedpaincausedbyspinalstimulation.thebehaviorof.Animalstudieshavefoundthatpregabalinmayhaveadvantageswhencombinedwithopioids.Pregabalinprovidesanewoptionfortheclinicaltreatmentofneuropathicpain.MechanismPregabalinmayreducethecalcium-dependentreleaseofsomeneurotransmittersbymodulatingcalciumchannelfunction.Althoughpregabalinisastructuralderivativeoftheinhibitoryneurotransmittergamma-aminobutyricacid(GABA),itdoesnotdirectlybindtoGABAA,GABABorbenzodiazepinereceptorsanddoesnotincreaseGABAAinculturedneuronsinvitroreaction,doesnotchangetheGABAconcentrationintheratbrain,andhasnoacuteeffectonGABAuptakeordegradation.However,studieshavefoundthatwhenneuronsculturedinvitroareexposedtopregabalinforalongtime,GABAtransporterdensityandfunctionalGABAtransportrateincrease.Pregabalindoesnotblocksodiumchannels,hasnoactivityonopioidreceptors,doesnotaltercyclooxygenaseactivity,hasnoactivityondopamineandserotoninreceptors,anddoesnotinhibittheregenerationofdopamine,serotoninornorepinephrine.ingest.PharmacokineticsAbsorption:Pregabalinisrapidlyabsorbedwhentakenonanemptystomach,reachingpeakplasmaconcentrationwithin1houraftersingleormultipledoses.Theoralbioavailabilityofpregabalinisestimatedtobe≥90%andisindependentofdose.Aftermultipledoses,steadystateisachievedwithin24to48hours.Whentakenwithfood,therateofabsorptionofpregabalinisreduced,withCmaxreducedby25-30%andtmaxdelayedtoapproximately2.5hours.However,takingpregabalinwithfooddoesnothaveaclinicallymeaningfuleffectontheextentofpregabalinabsorption.Distribution:Preclinicalstudieshaveshownthatpregabalincancrosstheblood-brainbarrierinmice,rats,andmonkeys.Pregabalincrossestheplacentaofratsandappearsinthemilkoflactatingrats.Inhumans,theapparentvolumeofdistributionofChemicalbookpregabalinafteroraladministrationisapproximately0.56L/kg.Pregabalindoesnotbindtoplasmaproteins.Metabolism:Themetabolismofpregabalininthehumanbodyisnegligible.Afteradministrationofradiolabeledpregabalin,approximately98%ofpregabalinisrecoveredintheurineinunchangedform.Themainmetaboliteofpregabalin,N-methylatedderivatives,wasalsofoundinurine,accountingfor0.9%oftheadministereddose.Inpreclinicalstudies,noracemizationeffectwasfoundintheconversionofpregabalinfromtheS-enantiomertotheR-enantiomer.Excretion:Pregabalinisprimarilyeliminatedfromthesystemiccirculationandexcretedviathekidneysasunchangeddrug.Themeaneliminationhalf-lifeofpregabalinis6.3hours.Bothplasmaandrenalclearanceofpregabalinaredirectlyproportionaltocreatinineclearance.Forpatientswithreducedrenalfunctionorwhoarereceivinghemodialysis,doseadjustmentmaybenecessaryClinicalapplicationInDecember2008,theU.S.FoodandDrugAdministration(FDA)approvedpregabalin(tradename"Lerrica")forthetreatmentofdiabeticperipheralneuralgia(DPN)andpostherpeticneuralgia(PHN).Themostcommonformofneuropathicpain.Neuropathicpainisoneofthemostdifficulttotreatchronicpainsyndromes.Itischaracterizedbydullpain,burning,andtinglingpain.Therearemanycausesofneuralgia.Diabetes,infection(suchasherpeszoster),cancer,andAIDScanallcauseneuralgia.About3%ofthepopulationinEuropesuffersfromneuralgia.medicineinteractions1.NotmetabolizedbythecytochromeP450system,therefore,itrarelyinteractswithotherdrugs.Itdoesnotaffectthepharmacokineticsofanti-epilepticdrugs(suchassodiumvalproate,phenytoin,lamotrigine,carbamazepine,phenobarbital,topiramate),oralcontraceptives,oralhypoglycemicdrugs,diuretics,insulin,etc.2.Whenthisproductisusedtogetherwithoxycodone,itsrecognitionfunctionisreducedandmotorfunctionimpairmentisenhanced.3.Ithasadditiveeffectswithlorazepamandethanol.resolveresolutionDiethylmalonateand3-methylbutyraldehydewerecondensedinthepresenceofdiisopropylaminetogive98.ThelatterundergoesdoublebondadditionwithKCNandishydrolyticallydecarboxylatedtoobtainracemicpregabalin96.RacemicpregabalinformsdiastereomericsaltswithS-(+)-mandelicacidandundergoescrystallizationresolutiontoobtaintheopticallypureS-isomer.capsulepreparationThepreparationmethodofpregabalincapsuleshasthefollowingsteps:①Passthepregabalinrawmaterialsthrougha30-mesh(porediameter600μm)sieveontheswinggranulator,andthenpassthepregabalinrawmaterialsthroughthe30-meshsievethrougha60-mesh(porediameter250μm)sieveandan80-mesh(porediameter180μm)sieveinsequence.,takethepregabalingranularpowderthathaspassedthroughthe60meshsieveandthepregabalingranularpowderthathasnotpassedthroughthe80meshsieve,andsetaside;②Passthelactosethroughthe80mesh(porediameter180μm)and120mesh(porediameter120μm)sievesinsequenceonthevibratingsieve,andtakethelactosegranularpowderthathaspassedthe80meshsieveandthelactosepowderthathasnotpassedthe120meshsieveandsetaside;③Firstmixthepregabalingranularpowderobtainedinstep①(D50particlesizeis180μm~220μm,D90particlesizeis250μm~280μm)andthebinderonamulti-directionalmotionmixer,thenaddlubricantandstep②toobtainLactosegranulepowder(D50particlesizeis120μm~140μm,D90particlesizeis160μm~180μm),continuetomixevenly,andfinallytheevenlymixedmaterialsaredirectlyfilledonafullyautomaticcapsulefillingmachinetoobtainpregabalincapsules.