3. Μοριακοί στόχοι φαρμάκων 2013

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Transcript of 3. Μοριακοί στόχοι φαρμάκων 2013

  • , , , -,

    , ,

    M

  • -

  • John Newport Langley (1852-1925) Paul Ehrlich (1854-1915)

    /

    /

    (receptive)

    (lateralchains, receptors)

    -

  • H

  • -

    . Ligand gated ion channel receptorsB. G-protein coupled receptors (GPCR). nzyme-linked receptors. Intracellular receptors

  • . - (Ligand gated ion channel receptors)

    (cys-loop) 5 (2) . , GABAA, GABAC, , 5-HT3

    4 . NMDA, AMPA,

  • ( )

    o . (ature, 2009)

    - : (bungarotoxin): ( )

  • GABA

    ( )

    GABAA

    GABA

    PKA

  • Y NMDA

  • NMDA ,

    2 AMPA : Na+, +NMDA : Na+, Ca2+

  • -

    - a+, Ca2+

    5-HT3

    - Cl-

    GABA

  • ( )

    -

  • B. G- (G-protein coupled receptors, GPCRs)

    1% , , , , ,

    (1, 2, 2, 1, 2, 3) (D1, D2, D3) (m1-m5) (5-HT1, 5-HT2, 5-HT4 5-HT7)

    7 (ransmembrane)

  • G-

    (binding pocket) 3

    GPCR

    ()

    Asp 113 2 Asp 117 3

    G

  • GPCR

    (effector)

    cAMP

    ( )

  • GPCR

    (effector) C

    IP3

    DAG

  • GPCR

  • .. PKA (negative feed-back)

  • (Atropa belladonna) ( )

    ( )

  • .

    2 :

  • .

    ..

    .. D3

    ..

  • Hsp70Hsp70

    HBD: Hormone Binding DomainNTD: Nuclear Translocation DomainHRE: Hormone Response Element

  • - (ligand gated ion channel receptors)

    G (G-protein coupled receptors, GPCRs )

    (enzyme-linked receptors)

    (intracellular receptors)

  • / -

  • - (voltage gated ion channels)

    Na+ Ca2+ K+

    -

  • -

    a+, Ca2+

    +

  • ()

    - (msec)- ( msec)

    - +

  • Na+

    S

    10 nM: , .

    1000 nM:

    .

  • Na+

    Na+

    .

    Na+

  • - Ca2+

    4 (L, N, P, T). L (large):

    - Ca2+

    DHP: (.. )

    PAA: (.. )

  • - K+

    ICa

    + (transient outward K+ channels, Ito) 4--

    + (delayed rectifier K+ channels, Ikr) --

    + (inward rectifier K+ channels, Iki)

    Ito Ikr

    Iki

    INa

  • / -

    -

  • . Na+/K+ ATP

    .

    .

  • . Na+/K+ ATP

    a+ Ca2+

  • .

  • SSRIs (Prozac), TCA

    ,

    (GABA) Gabatril

  • K -

  • .

    . -

    .

    . P

    V. ( )

  • ()

    14.000 /sec

    . -

  • . -

    A Physostigma venenosum Calabar Clermont

  • . -

    M - - (, DPF) (, )

    DPF

  • .

    () (, , 5--)

    (, Inhibitors of Monoaminoxidases)

    - ( ) : ()

    - () : (Parkinson, Alzheimer)

  • Mitogen-Activated Protein Kinases ()

    . P

  • - in vitro

    - /II

    p38( )

    p38 , , IL-1, TNF-a

    15 48 p38

    . P

  • V.

    ( Camptotheca accuminata) (Mandragora officinarum)

  • -

  • .

    1. A : D

    .. , ,

    2. : D

    .. , ,

    3. : DNA RNA

    ..

  • 1.A

    ()

    G-C

  • 2.

  • 3.

    (6-TG)

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