Pregabalin
Pregabalin ha se GABAA kapa GABAB receptor agonist.
Pregabalin ke gabapentinoid mme e sebetsa ka ho thibela dikanale tse itseng tsa calcium.Haholo-holo ke ligand tsa sebaka sa tlatsetso sa α2δ sa likanale tse itseng tsa khalsiamo tse itšetlehileng ka voltage (VDCCs), 'me ka hona se sebetsa e le sethibela sa α2δ subunit-containing VDCCs.Ho na le li-subunits tse peli tsa α2δ tse tlamang lithethefatsi, α2δ-1 le α2δ-2, 'me pregabalin e bonts'a kamano e tšoanang bakeng sa (ka hona ho haella ha khetho pakeng tsa) libaka tsena tse peli.Pregabalin e khetha ho tlamahaneng ha eona ho subunit ea α2δ VDCC.Ho sa tsotellehe hore pregabalin ke analogue ea GABA, ha e tlame ho li-receptor tsa GABA, ha e fetohe GABA kapa e 'ngoe ea GABA receptor agonist ka vivo,' me ha e fetole ka ho toba lipalangoang tsa GABA kapa metabolism.Leha ho le joalo, pregabalin e fumanoe e hlahisa keketseho e itšetlehileng ka lethal dose ho polelo ea boko ea L-glutamic acid decarboxylase (GAD), enzyme e ikarabellang bakeng sa ho kopanya GABA, ka hona e ka ba le litlamorao tse sa tobang tsa GABAergic ka ho eketsa maemo a GABA bokong.Hona joale ha ho na bopaki ba hore liphello tsa pregabalin li fetisetsoa ke mochine ofe kapa ofe ntle le ho thibela li-VDCC tse nang le α2δ.Ho latela, thibelo ea li-VDCC tse nang le α2δ-1 ka pregabalin e bonahala e ikarabella bakeng sa litlamorao tsa eona tsa anticonvulsant, analgesic, le anxiolytic.
Li-endogenous α-amino acids L-leucine le L-isoleucine, tse batlang li tšoana hantle le pregabalin le li-gabapentinoids tse ling ka sebopeho sa lik'hemik'hale, ke li-ligands tsa α2δ VDCC subunit e nang le kamano e tšoanang le ea gabapentinoids (mohlala, IC50 = 71 nM bakeng sa L- isoleucine), 'me li teng ka mokelikeli oa cerebrospinal oa motho maemong a micromolar (mohlala, 12.9 μM bakeng sa L-leucine, 4.8 μM bakeng sa L-isoleucine).Ho 'nile ha boleloa hore e ka' na ea e-ba li-ligands tse sa feleng tsa subunit le hore li ka 'na tsa hanyetsa liphello tsa gabapentinoids ka tlhōlisano.Ho latela, le ha li-gabapentinoids joalo ka pregabalin le gabapentin li na le li-nanomolar affinities bakeng sa α2δ subunit, matla a tsona a vivo a maemong a tlase a micromolar, mme tlholisano ea ho tlama li-amino acid tsa endogenous ho boletsoe e ka ba eona e ikarabellang bakeng sa phapang ena.
Pregabalin e fumanoe e na le kamano e phahameng ka makhetlo a 6 ho feta gabapentin bakeng sa α2δ e nang le li-VDCC tse nang le subunit thutong e le 'ngoe.Leha ho le joalo, phuputso e 'ngoe e fumane hore pregabalin le gabapentin li ne li e-na le likamano tse tšoanang bakeng sa karoloana ea motho ea α2δ-1 (Ki = 32 nM le 40 nM, ka ho latellana).Leha ho le joalo, pregabalin e matla ka makhetlo a 2 ho isa ho a 4 ho feta gabapentin e le setlhare, 'me liphoofolong, e bonahala e le matla ka makhetlo a 3 ho isa ho a 10 ho feta gabapentin e le anticonvulsant.
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