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(nebival). 5 . . :
: ߧ֧ҧڧӧݧ (ѧݧ, ѧݧѡ-[ڧާڧߧҧڧ(ާ֧ڧݧ֧)ҧڧ[6--3,4-էڧԧڧէ]-2H-1-ҧ֧ߧ٧ڧѧ-2-ާ֧ѧߧ) ܧѧէڧ֧ݧ֧ܧڧӧߧ ҧݧܧѧ 1-ѧէ֧ߧ֧֧ ֧֧ԧ ܧݧ֧ߧڧ ӧѧ٧էڧݧѧڧڧާ ӧۧӧѧާ. ܧѧ٧ӧѧ֧ ѧߧڧԧڧ֧֧ߧ٧ڧӧߧ, ѧߧڧѧߧԧڧߧѧݧߧ ѧߧڧѧڧާڧ֧ܧ է֧ۧӧڧ. ֧էѧӧݧ֧ ҧ ѧ֧ާѧ էӧ ߧѧߧڧާ֧, ܧѧاէ ڧ ܧ ҧݧѧէѧ֧ ҧާ ӧۧӧѧާ. D-ߧ֧ҧڧӧݧ ӧݧ֧ ܧߧܧ֧ߧߧ ӧܧ֧ݧ֧ܧڧӧߧ ҧݧܧѧ 1-ѧէ֧ߧ֧֧ (էӧ 1-ѧէ֧ߧ֧֧ѧ 293 ѧ٧ ӧ, ֧ 2-ѧէ֧ߧ֧֧ѧ). ӧ٧ѧڧާէ֧ۧӧ֧ -ѧէ֧ߧ֧֧ѧާ. L-ߧ֧ҧڧӧݧ ܧѧ٧ӧѧ֧ ާԧܧ էѧڧ֧ է֧ۧӧڧ ٧ ֧ ާէݧڧ ӧӧҧاէ֧ߧڧ ֧ݧѧܧڧ֧ԧ ѧܧ ܧڧէ ѧ٧ (NO) ڧ ߧէ֧ݧڧ է. ߧڧԧڧ֧֧ߧ٧ڧӧߧ ֧ܧ ֧ѧѧ ҧݧӧݧ֧ ѧܧا ߧڧا֧ߧڧ֧ ѧܧڧӧߧ ֧ߧڧ-ѧߧԧڧ֧ߧ٧ڧߧӧ ڧ֧ާ (ߧ ܧ֧ݧڧ֧ ڧ٧ާ֧ߧ֧ߧڧ֧ ѧܧڧӧߧ ֧ߧڧߧ ݧѧ٧ާ ܧӧ). ҧݧѧէѧ֧ ѧߧڧѧԧ֧ԧѧߧ է֧ۧӧڧ֧, ާ֧ߧѧ֧ ѧէԧ֧٧ڧ ާҧڧ, ӧݧ ѧߧڧާҧڧ֧ܧڧ ֧ܧ. ߧڧاѧ֧ ֧ҧߧ ާڧܧѧէ ܧڧݧէ (֧ا֧ߧڧ ߧڧا֧ߧڧ ֧- ߧѧԧ٧ܧ ߧ ֧է). է ڧݧߧ ѧߧڧܧڧէѧߧ, ܧѧ٧ӧѧ֧ ѧߧԧڧ֧ܧߧ ѧߧڧѧ֧ܧݧ֧ڧ֧ܧڧ ֧ܧ. ߧڧѧڧާڧ֧ܧ է֧ۧӧڧ ҧݧӧݧ֧ߧ էѧӧݧ֧ߧڧ֧ ѧݧԧڧ֧ܧԧ ѧӧާѧڧ٧ާ ֧է ٧ѧާ֧էݧ֧ߧڧ֧ AV-ӧէڧާ. ߧڧاѧ֧ ӧ֧ߧߧ ܧ, ڧ٧ڧ֧ܧ ߧѧا֧ߧڧ ֧; ߧڧاѧ֧ ܧߧ֧ߧ էڧѧݧڧ֧ܧ էѧӧݧ֧ߧڧ ݧ֧ӧ ا֧ݧէܧ , էݧڧ֧ݧߧ ڧާ֧ߧ֧ߧڧ, ; ݧѧ֧ էڧѧݧڧ֧ܧ ߧܧڧ ֧է (ߧڧاѧ֧ էѧӧݧ֧ߧڧ ߧѧݧߧ֧ߧڧ), ӧ֧ݧڧڧӧѧ֧ ѧܧڧ ӧҧ. ߧڧاѧ֧ ѧ ا֧ ڧ ֧ߧܧѧէڧ ӧѧ֧ ֧֧ߧڧާ ڧ٧ڧ֧ܧ ߧѧԧ٧ܧ. ӧݧڧ֧ ߧ ݧڧڧէߧ ֧ܧ ӧ֧ߧ ԧݧܧ٧ ܧӧ, ߧ ҧݧѧէѧ֧ ڧާѧާڧާ֧ڧ֧ܧ ѧܧڧӧߧ. ߧڧԧڧ֧֧ߧ٧ڧӧߧ ֧ܧ ѧ٧ӧڧӧѧ֧ ֧֧ 2C5 էߧ֧, ѧҧڧݧߧ ֧ܧ ֧֧ 1C2 ާ֧ ڧާ֧ߧ֧ߧڧ. էݧڧ֧ݧߧ ֧ѧڧ (3 ԧէ) ݧ֧ѧߧߧ ߧ ѧ٧ӧڧӧѧ֧. ݧ ڧ֧ާ ӧߧ ߧ֧٧ѧӧڧڧާ ڧ֧ާ ڧ ҧ ѧҧҧڧ֧ . ڧէߧ ާ֧ѧҧݧڧ٧ ֧ѧѧ ֧է֧ݧ ԧ֧ߧڧ ѧڧ֧ߧ. ڧէߧ ѧӧݧ֧ ֧էߧ֧ 12% ݧڧ ҧ ާ֧ѧҧݧڧ٧ާ (֧ܧ ֧ӧڧߧԧ اէ֧ߧڧ ֧֧ ֧֧ߧ) 100% ݧڧ ާ֧էݧ֧ߧߧ ާ֧ѧҧݧڧ٧ާ. ѧܧڧާѧݧߧѧ ܧߧ֧ߧѧڧ ݧѧ٧ާ ܧӧ ݧڧ ҧ ާ֧ѧҧݧڧ٧ާ էڧԧѧ֧ ֧֧ߧڧ 24 , ԧڧէܧڧާ֧ѧҧݧڧ ֧֧ ߧ֧ܧݧܧ . ߧ֧ߧѧڧ ݧѧ٧ާ ܧӧ ѧӧݧ֧ 1C30 ާܧ/ ڧߧѧݧߧ է٧. ӧ٧ӧѧߧڧ ߧѧߧڧާ֧ ҧ֧ݧܧѧާ ݧѧ٧ާ ܧݧ 98%. ֧ѧҧݧڧ٧ڧ֧, ѧڧߧ ҧѧ٧ӧѧߧڧ֧ ѧܧڧӧߧ ԧڧէܧڧާ֧ѧҧݧڧ, ֧ ѧݧڧڧܧݧڧ֧ܧԧ ѧާѧڧ֧ܧԧ ԧڧէܧڧݧڧӧѧߧڧ, N-է֧ѧݧܧڧݧڧӧѧߧڧ, ԧݧܧߧڧӧѧߧڧ. ܧ ѧާѧڧ֧ܧԧ ԧڧէܧڧݧڧӧѧߧڧ ԧ֧ߧ֧ڧ֧ܧ ֧է֧ݧ֧ߧ ܧڧݧڧ֧ݧߧ ݧڧާڧ٧ާ ٧ѧӧڧڧ ڧ٧֧ާ֧ߧ ڧާ CYP 2D6. ֧ڧ ݧӧӧ֧է֧ߧڧ ߧѧߧڧާ֧ ߧ֧ҧڧӧݧݧ ݧڧ ҧ ާ֧ѧҧݧڧ٧ާ ѧӧݧ֧ ֧էߧ֧ 10 , ԧڧէܧڧާ֧ѧҧݧڧ 24 . ݧڧ ާ֧էݧ֧ߧߧ ާ֧ѧҧݧڧ٧ާ ֧ڧ ݧӧӧ֧է֧ߧڧ ߧѧߧڧާ֧ ӧ֧ݧڧڧӧѧ֧ 3C5 ѧ, ֧ڧ ݧӧӧ֧է֧ߧڧ ԧڧէܧڧާ֧ѧҧݧڧ ڧҧݧڧ٧ڧ֧ݧߧ 2 ѧ٧. ӧէڧ ܧѧާ (38%) ܧڧ֧ߧڧܧ (48%). ѧާѧܧܧڧߧ֧ڧ֧ܧڧ ѧѧާ֧ ߧ ڧާ֧ ӧ٧ѧߧ ݧӧ ѧ٧ݧڧڧ. : ; ߧڧ֧ܧѧ ֧է֧ߧѧ ߧ֧էѧߧ ( ܧާҧڧߧѧڧ ڧߧԧڧҧڧѧާ , էڧ֧ڧܧѧާ, ѧߧѧԧߧڧѧާ ѧߧԧڧ֧ߧ٧ڧߧ II /ڧݧ ֧ѧѧѧާ ߧѧ֧ߧܧ). : ӧ٧ݧ ӧߧ, 1 ѧ ܧ էߧ ا ӧ֧ާ (ا֧ݧѧ֧ݧߧ ) ߧ֧٧ѧӧڧڧާ ڧ֧ާ ڧ, ߧ ѧ٧ا֧ӧӧѧ էѧߧ ܧݧڧ֧ӧ اڧէܧ. ֧ڧѧݧߧѧ ԧڧ֧֧ߧ٧ڧ. ֧էߧ ߧѧ է٧ ѧӧݧ֧ 2,5C5 ާ (1/2C1 ѧҧݧ֧ܧ). ѧܧڧާѧݧߧѧ ߧѧ է٧ 10 ާ. ҧݧߧ ֧ߧ ߧ֧էѧߧ ѧڧ֧ߧ ӧ٧ѧ ѧ 65 ݧ֧ ߧѧѧݧߧѧ ߧѧ է٧ ѧӧݧ֧ 2,5 ާ (1/2 ѧҧݧ֧ܧ). ߧڧ֧ܧѧ ֧է֧ߧѧ ߧ֧էѧߧ. ѧѧݧߧѧ է٧ ѧӧݧ֧ 2,5 ާ/ (1/2 ѧҧݧ֧ܧ). ٧ѧӧڧڧާ ֧֧ߧڧާ ֧ܧڧӧߧ ߧѧ է٧ ާا֧ ҧ ֧֧ߧߧ, ڧߧ֧ӧѧݧ 14 էߧ֧, ӧ֧ݧڧ֧ߧ է 5 ާ (1 ѧҧݧ֧ܧ) էڧ ڧ֧. : ӧ֧ߧߧѧ ӧӧڧ֧ݧߧ ܧާߧ֧ߧѧ ֧ѧѧ, ѧ֧ڧѧݧߧѧ ԧڧ֧ߧ٧ڧ, ߧڧ֧ܧѧ ֧է֧ߧѧ ߧ֧էѧߧ ѧ٧ է֧ܧާ֧ߧѧڧ, ѧߧԧڧѧڧ֧ܧѧ ֧ߧܧѧէڧ (֧ߧܧѧէڧ ڧߧާ֧ѧݧ), ܧѧէڧԧ֧ߧߧ , ӧѧا֧ߧߧѧ ҧѧէڧܧѧէڧ ( ާ֧ߧ֧ 50 ./ާڧ), ڧߧէ ݧѧҧ ڧߧߧԧ ٧ݧ, AV-ҧݧܧѧէ IICIII ֧֧ߧ; ; ֧ާڧާ, ا֧ݧ ߧѧ֧ߧڧ ߧܧڧ ֧֧ߧ; ҧݧڧ֧ڧڧ ٧ѧҧݧ֧ӧѧߧڧ ֧ڧ֧ڧ֧ܧڧ է (ڧߧէ ֧֧ާ֧اѧ֧ۧ ާ); ާڧѧ֧ߧڧ, ާ֧ߧѧ ݧѧҧ; է֧֧ڧ; էߧӧ֧ާ֧ߧߧ / ӧӧ֧է֧ߧڧ ӧ֧ѧѧާڧݧ; ڧާ֧ߧ֧ߧڧ ӧ٧ѧ է 18 ݧ֧. : ߧ ֧է֧ߧ-էڧ ڧ֧ާ: ҧѧէڧܧѧէڧ, ѧڧ֧ܧѧ ԧڧ֧ߧ٧ڧ, էܧ, ֧ܧ, ֧է֧ߧѧ ߧ֧էѧߧ, AV-ҧݧܧѧէ, ߧѧ֧ߧڧ ڧާ ֧է, ڧߧէ ֧ۧߧ, ܧѧէڧѧݧԧڧ. ߧ ߧ֧ӧߧ ڧ֧ާ: ԧݧӧߧѧ ҧݧ, ԧݧӧܧا֧ߧڧ, է֧֧ڧ, ѧݧ, ѧ֧֧٧ڧ, ߧڧا֧ߧڧ ҧߧ ܧߧ֧ߧѧڧ ӧߧڧާѧߧڧ, ߧݧڧӧ, ҧ֧ߧߧڧ, ܧާѧߧ ߧӧڧէ֧ߧڧ, ԧѧݧݧڧߧѧڧ. ߧ ڧ֧ӧѧڧ֧ݧߧ ڧ֧ާ: ߧ, ٧ѧ, էڧѧ֧, ӧ . ݧݧ֧ԧڧ֧ܧڧ ֧ѧܧڧ: ܧاߧѧ . ڧ: ҧߧѧ٧ ( ڧݧ ӧڧ ҧܧڧӧߧ ٧ѧҧݧ֧ӧѧߧڧ ݧ֧ԧܧڧ ѧߧѧާߧ֧٧), է֧ާѧ, ԧڧ֧ԧڧէ, ڧߧڧ. : c اߧ ֧ѧѧ ߧѧ٧ߧѧѧ ֧ߧ ߧ֧էѧߧ, ݧ֧֧ߧڧ ѧڧ֧ߧ ѧ 65 ݧ֧ (ߧ֧ҧէڧާ ܧߧݧڧӧѧ ߧܧڧ ֧ 1 ѧ 4C5 ާ֧), ѧѧߧ էڧѧҧ֧ (ާԧ ާѧܧڧӧѧ ڧ٧ߧѧܧ ԧڧԧݧڧܧ֧ާڧ), ԧڧ֧ߧܧڧ ڧӧڧէߧ ا֧ݧ֧٧ (ާѧܧڧ֧ ѧڧܧѧէڧ), ѧݧݧ֧ԧڧ֧ܧڧ ٧ѧҧݧ֧ӧѧߧڧ (ӧ٧ާاߧ ڧݧ֧ߧڧ ѧߧѧڧݧѧܧڧ֧ܧڧ ֧ѧܧڧ) ڧѧ٧ (ߧѧ٧ߧѧ֧ߧڧ ӧ٧ާاߧ, ֧ݧ اڧէѧ֧ާ ֧ܧ ֧ѧڧ ֧ӧѧ֧ ֧ߧڧѧݧߧ ڧ էݧ ѧڧ֧ߧ). ߧڧڧߧ ߧڧ ѧڧ֧ߧ, ڧߧڧާѧڧ ֧ѧѧ, ӧܧݧѧ֧ ߧѧҧݧէ֧ߧڧ ӧߧ ( ߧѧѧݧ ݧ֧֧ߧڧ ֧ا֧էߧ֧ӧߧ, ٧ѧ֧ 1 ѧ 3C4 ާ֧), ӧߧ ԧݧܧ٧ ܧӧ ҧݧߧ ѧѧߧ էڧѧҧ֧ (1 ѧ 4C5 ާ֧), ߧܧڧ ֧ ѧڧ֧ߧ اڧݧԧ ӧ٧ѧ (1 ѧ 4C5 ާ֧), ߧڧ ֧ڧ֧ڧ֧ܧԧ ܧӧҧѧ֧ߧڧ. ֧ڧ ҧ֧֧ާ֧ߧߧ ܧާݧ֧ߧڧ ԧէ ߧѧ٧ߧѧѧ ݧܧ ԧ ܧѧ٧ѧߧڧ, ܧߧݧ֧ ӧѧ. ֧֧ߧڧ ݧ֧է֧ ֧ӧѧ ٧ 48C72 է է. ݧѧ ܧԧէ ߧ֧ӧ٧ާاߧ, ߧ֧ҧէڧާ ҧ֧֧ڧ ԧ ߧѧҧݧէ֧ߧڧ ٧ ߧӧاէ֧ߧߧާ ֧֧ߧڧ 48C72 (ӧ٧ާاߧ ѧ٧ӧڧڧ ҧѧէڧܧѧէڧ, ѧ֧ڧѧݧߧ ԧڧ֧ߧ٧ڧ, ԧڧԧݧڧܧ֧ާڧ, ԧߧ֧֧ߧڧ էѧߧڧ). ֧ܧѧѧ ݧ֧֧ߧڧ ݧ֧է֧ ֧֧ߧߧ, ߧڧاѧ է٧ ֧֧ߧڧ 10 էߧ֧, ݧ֧֧ߧڧ ֧ߧܧѧէڧ ֧֧ߧڧ 1C2 ߧ֧. ܧڧݧڧܧ ֧ܧڧӧߧ ֧ѧѧ ߧڧاѧ֧. ݧߧ, ݧ٧ڧ֧ ܧߧѧܧߧާ ݧڧߧ٧ѧާ, էݧاߧ ҧ ֧է֧اէ֧ߧ ӧ٧ާاߧ ާ֧ߧ֧ߧڧ էܧڧ ݧ֧٧ߧ اڧէܧ. ֧ҧڧӧݧ ߧ ӧݧڧ֧ ߧ ڧާߧ ֧ѧܧڧ, էߧѧܧ ӧݧߧ֧ߧڧ ֧ߧڧѧݧߧ ѧߧ ӧڧէ է֧֧ݧߧ ݧ֧է֧ ڧӧѧ ӧ٧ާاߧ ӧ٧ߧڧܧߧӧ֧ߧڧ ҧߧ ֧ѧܧڧ ߧ ߧ֧ӧߧ ڧ֧ާ. : ӧ٧ާاߧ ӧ֧ߧڧ ѧߧڧԧڧ֧֧ߧ٧ڧӧߧԧ ֧ܧ ֧ѧߧߧ ڧާ֧ߧ֧ߧڧ էԧڧާ ѧߧڧԧڧ֧֧ߧ٧ڧӧߧާ ֧էӧѧާ ߧڧԧݧڧ֧ڧߧ; ҧ اߧ ݧ֧է֧ ҧݧէѧ ֧ѧߧڧ ѧ٧٧ڧߧ. ݧܧѧ ާ֧էݧ֧ߧߧ ܧѧݧڧ֧ӧ ܧѧߧѧݧ (ӧ֧ѧѧާڧ էڧݧڧѧ٧֧) ڧݧڧӧѧ ԧߧ֧֧ߧڧ AV-ӧէڧާ; ѧߧڧѧڧާڧ֧ܧڧ ֧էӧ, ֧٧֧ڧ, -ާ֧ڧݧէ, ܧݧߧڧէڧ, ԧѧߧѧڧ ӧѧا֧ߧߧ ҧѧէڧܧѧէڧ; ѧߧ֧֧٧ڧڧ ֧էӧ ܧѧէڧէ֧֧ڧӧߧ ֧ܧ ӧ֧ߧڧ֧ ڧܧ ѧ٧ӧڧڧ ѧ֧ڧѧݧߧ ԧڧ֧ߧ٧ڧ. ӧާ֧ߧ ڧާ֧ߧ֧ߧڧ ֧է֧ߧާ ԧݧڧܧ٧ڧէѧާ ӧ٧ާاߧ ާާѧڧ ڧѧ֧ݧߧԧ ߧߧԧ էާߧԧ ֧ܧ. ݧߧڧէڧ ڧݧڧӧѧ֧ ڧߧէ ާ֧ߧ. ߧէܧ ާڧܧާѧݧߧԧ ܧڧݧ֧ߧڧ (ڧѧާڧڧ, ҧѧҧڧѧ) ߧڧاѧ, ڧߧԧڧҧڧ ާڧܧާѧݧߧԧ ܧڧݧ֧ߧڧ (ڧާ֧ڧէڧ) ӧѧ ܧߧ֧ߧѧڧ ߧ֧ҧڧӧݧݧ ݧѧ٧ާ ܧӧ. ֧ѧѧ ߧ ֧ߧڧ֧ է֧ۧӧڧ ڧߧݧڧߧ ֧ѧݧߧ ԧڧԧݧڧܧ֧ާڧ٧ڧڧ ֧է, էߧѧܧ ާا֧ ާѧܧڧӧѧ ߧ֧ܧ ڧާާ ԧڧԧݧڧܧ֧ާڧ (ѧڧܧѧէڧ). էߧӧ֧ާ֧ߧߧ ڧ֧ ѧݧܧԧݧ, ֧ާڧէ ڧݧ ԧڧէݧڧѧ٧ڧէ ߧ ܧѧ٧ӧѧ ӧݧڧߧڧ ߧ ѧާѧܧܧڧߧ֧ڧܧ ߧ֧ҧڧӧݧݧ. ֧ҧڧӧݧ ߧ ӧݧڧ֧ ߧ ѧާѧܧܧڧߧ֧ڧܧ ѧާѧܧէڧߧѧާڧܧ ӧѧѧڧߧ. էߧӧ֧ާ֧ߧߧ ߧѧ٧ߧѧ֧ߧڧ ڧڧܧݧڧ֧ܧڧ ѧߧڧէ֧֧ѧߧ, ҧѧҧڧѧ ڧ٧ӧէߧ ֧ߧڧѧ٧ڧߧ ާا֧ ӧѧ ԧڧ֧ߧ٧ڧӧߧ ֧ܧ ֧ѧѧ. : ڧާާ: ӧ, ߧ, ڧѧߧ, ԧڧ֧ߧ٧ڧ, ҧߧѧ٧, ڧߧӧѧ ҧѧէڧܧѧէڧ, AV-ҧݧܧѧէ, ֧է֧ߧѧ ߧ֧էѧߧ, ܧѧէڧԧ֧ߧߧ , ֧ ٧ߧѧߧڧ, ܧާ, ѧߧӧܧ ֧է. ֧֧ߧڧ: ާӧѧߧڧ ا֧ݧէܧ, ߧѧ٧ߧѧ֧ߧڧ ѧܧڧӧڧӧѧߧߧԧ ԧݧ. ӧѧا֧ߧߧ ѧ֧ڧѧݧߧ ԧڧ֧ߧ٧ڧ, ҧѧէڧܧѧէڧ ا֧ݧ ֧է֧ߧ ߧ֧էѧߧ ӧӧ֧է֧ߧڧ ڧߧ֧ӧѧݧ 2C5 ާڧ ‑ѧէ֧ߧڧާݧ է էڧا֧ߧڧ ا֧ݧѧ֧ާԧ ֧ܧ, ӧڧ ݧاڧ֧ݧߧԧ ֧ܧ ֧ݧ֧ҧѧ٧ߧ ӧӧ֧է֧ߧڧ էѧާڧߧ, էҧѧާڧߧ ڧݧ ߧڧߧ֧ڧߧ. ܧѧ֧ӧ ݧ֧էڧ ާ֧ ߧѧ٧ߧѧ֧ߧڧ 1C10 ާ ԧݧܧѧԧߧ ڧݧ ѧߧӧܧ ѧߧӧ֧ߧ٧ߧԧ ڧߧѧܧѧէڧѧݧߧԧ ݧ֧ܧڧާݧ. ҧߧѧ٧ާ ߧѧ٧ߧѧѧ ڧާݧ 2-ѧէ֧ߧ֧֧ /; ا֧ݧէܧӧ ܧѧڧݧڧ ݧڧէܧѧڧ (ѧߧڧѧڧާڧ֧ܧڧ ֧ѧѧ I ܧݧѧ ӧӧէڧ ߧ֧ݧ٧); ѧ٧ӧڧڧ է էڧѧ٧֧ѧ /. : , ٧ѧڧ֧ߧߧ ӧ֧ ާ֧ ֧ާ֧ѧ է 25 㧳.