Tadalafil kua teeyog ib daim ntawv ua kua ntawm tadalafil ua kom tau siv rau kev kho mob xws li erectile kawg ntshav siab (PAH), lossis benign prostatic hyperplasia (bpph). Nws txhim kho txoj kev ua kom cov leeg ua kom tiav los ntawm cov oxium thiab tsis muaj) los ntawm kev cuam tshuam PDRadation PDRadation pyclic ntawm guanosine monoposphate (CGMP). Nyob rau hauv lub cornus cavernosum ntawm tus noov, cov tshuab no tuaj yeem nce cov ntshav txaus thiab pab txiv neej ua kom lub cev muaj kev sib deev; Hauv kev ntshaav hauv plab, nws tuaj yeem txo cov vasliary vascular tsis kam thiab txhim kho lub peev xwm ntawm cov neeg mob ntsws kom tawg. Cov tshuaj no sib txawv ntawm cov ntsiav tshuaj ib txwm nyob hauv qhov ntawd nws yog hauv cov kua ua kua, uas ua rau cov pab kho kom haum thiab kho tus kheej. Kev npaj ua kua tuaj yeem hla cov txheej txheem digestive ntawm cov plab zom mov thiab ua kom pom kev tsis pom lub sijhawm ntawm cov tshuaj. Yog li ntawd, lawv feem ntau yog nruab nrog cov quav lossis cov koob txhaj tshuaj rau cov neeg mob ntsuas thiab nqa lawv tus kheej.
Peb Cov Khoom
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Cov ntaub ntawv ntxiv ntawm kev sib txuas lus:
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Tadalafil COA
Puzzle ntawm Tadalafil Kua Dauv Dauv Mechanism: Ntau lub luag haujlwm ntawm CGMP hauv lub paj hlwb
Tadalafil kua tee, raws li ib tug sawv cev siv tshuaj ntawm phosphodiesterase 5 (PDE5) Aibitors, muaj qhov ua rau muaj kev cuam tshuam ntawm CGMP hauv lub cev nqaij hlav Txhawb txoj kev vascular dilation thiab ntshav txaus, thiab thaum kawg ua tiav kev txhim kho hauv kev ua haujlwm erectile. Txawm li cas los xij, nrog cov kev tshawb nrhiav ntawm neuroscience, ntau lub luag haujlwm ntawm CGMP hauv qhov tseem ceeb me me rau kev tswj hwm neural, kev ua haujlwm lub cev muaj zog, thiab txawm tias kev mob hlwb.
Synthesis thiab kev tsis zoo ntawm CGMP: molecular transdlees hauv neural teeb liab transduction
Cov synthesis ntawm CGMP: Ib txoj kab li ob zaug los ntawm tsis muaj / GC rau Natriuretic Peptide / SGC
Lub sijhawm ntawm CGMP feem ntau yog nyob ntawm ob hom Guanlate Cyclase (GC) enzymes:
Soluble Guanylate Cyclase (SGC): Raws li ib tug receptor rau nitric oxide (tsis muaj), sgc catalyzes kev hloov pauv ntawm GPMP thaum tsis muaj khi. Txoj kev no tau dav nyob hauv cov paj hlwb, piv txwv li, hauv hippocampus, tsis muaj kev tswj hwm synaptic los ntawm SGC / CGMP txoj kev; Hauv Purkhiav cov hlwb ntawm CGMELUM, CGMP PKG (protein kinase g) txoj kev g) txoj kev yog koom nrog hauv kev tswj xyuas cov kev sib koom tes zoo.
Granular Guananlate cyclase (PGC): Ua haujlwm los ntawm Natriuretic Peptels thiab BNC yog tshaj tawm hauv cov ntshav ntawm Cerebruminal Kua tiam thiab ntshav {}} lub hlwb muaj nuj nqi. Nyob rau hauv xyoo tas los, kev tshawb fawb tau pom tias kev txawv txav hauv natriuretic peptace
Kev ua rau ntawm CGMP: cov "molecular txiab" ntawm PDE tsev neeg
Ib nrab - lub neej ntawm CGMP yog luv heev (feem ntau<1 second), and its degradation is mainly accomplished by the phosphodiesterase (PDE) family. In the brain, PDE5, PDE2, and PDE9 are the main enzymes that degrade cGMP:
PDE5: Dav faib dav hauv hippocampus, cortex, thiab striatum, nws yog lub hom phiaj tseem ceeb ntawm Tadalafil. Kev inhibition ntawm PDE5 tuaj yeem ntev ntev lub sijhawm ntawm CGMP kev piav qhia thiab txhim kho synaptic kis tau txais txiaj ntsig.
Pde2: Ib txhij ntawm CGMP thiab chaw pw hav zoov, thiab yog qhia heev nyob rau hauv Oldfory Cov Teeb thiab Hippocampus. PDE2 Inhibitors tuaj yeem txhim kho kev txawj ntse los ntawm kev tswj CGMP / Camp Hla {}} hais.
PDE9: Kev cuam tshuam tshwj xeeb ntawm CGMP, overexpressed hauv hippocampus thiab Cortex ntawm Ad cov neeg mob, tuaj yeem koom nrog qhov tsis nco qab qhov tsis zoo ntawm CGMP kev txwv tsis taus CGMP.
Cov chaw kuaj mob insights: tadalafil kua tee bypass thawj metabolism ua ntej cov metabolism tom ntej los ntawm kev nqus dej, kom ntau cov tshuaj tiv thaiv ntshav siab. Nws cov nyhwm nyhuv ntawm Pde5 tsis txwv rau cov hlab ntshav peripheral, tab sis kuj tseem tuaj yeem cuam tshuam rau cov ntshav hauv plawv ciam av los ntawm ntshav (BBB). Cov yeeb yam no muab txoj hauv kev tshiab rau kev kho cov kab mob nurodegenerative.
Cov tub ntxhais muaj nuj nqi ntawm CGMP hauv lub hlwb: Cov kev cai tswj hwm network los ntawm molecules rau kev coj cwj pwm
Synaptic Yas thiab Kev Kawm thiab Nco: CGMP li 'Nco Molecule'
Lub hippocampus yog thaj chaw tseem ceeb rau kev kawm thiab lub cim xeeb, thiab nws lub zog synaptic (xws li LETP) nyob ntawm CGMP kev piav qhia:
Nmda receptor ua kom tiav: tom qab glutamate khi rau NMDA recetors, nws accodulin o synthe (nnos) los ntawm sgc, thaum kawg nce CGMP qib.
PKG phosphorylation hom phiaj protein: Tom qab CGMP activates PKG, nws phosphorallates ampein1, txhawb nws txoj kev nkag mus rau hauv postsynaptic thiab txhim kho synaptic kis tau zoo. Cov kev sim tsiaj tau pom tias txhaj CGMP analogs rau hauv hippocampus tuaj yeem txhim kho kev muaj peev xwm kho spatial card.
Cov ntaub ntawv pov thawj kho mob: Ob lub - Dig Muag Sim Cov Neeg Mob Me Me (McM
Kev Ua Kom Muaj Kev Tsav Tsheb thiab Cerebellar Muaj nuj nqi: CGMP tswj hwm 'lub cev tshuav'
Puab hlwb hlwb nyob rau hauv cerebellum yog cov neurons tseem ceeb rau lub cev muaj zog, thiab lawv cov kab ke CGMP taw qhia txoj hauv kev tshwj xeeb:
Crawling Fiber Parallel fiber ntau cov tswv yim fiber ntau zog: thaum nkag fiber ntau cov lus qhia, CGMP tswj hwm cell, CGMP tswj hwm ntawm tes Yog tias cov txheej txheem no tsis zoo, nws tuaj yeem ua rau Ataxia (xws li spycolepellar ataxia, sca).
Cov Qauv Tsiaj Kawm: Hauv cov qauv Sca1, CGMP qib hauv Purkoj tau raug txo qis, qhia tias CGMP kev piav qhia yog qhov kev kho mob.
Kev kos duab kos duab hloov chaw: Qhov "lub teeb rhiab" ntawm CGMP
Txawm hais tias lub retina tsis muaj nyob rau cov tsoos "lub hlwb", nws CGMP kev piav mechanism yog cov homologous zoo rau cov leeg nruab nrab:
Qws xov tooj hloov chaw: Hauv qhov tsaus ntuj, CGMP tswj hwm qhov kev qhib ntawm lub collic nucleotide gated cells, cia na infllex thiab tsim kom muaj 'tsaus nti tam sim no'. Tom qab lub teeb ua zog ua kom zoo, PDE tau qhib los ntawm g protein (transducin), tsis pom zoo cgmp thiab kaw cov channel, ua rau cell hyperpolarization.
Cov kev saib xyuas qhov tseeb: retrigrant PDE6 kev sib pauv yog ib qho kev ua haujlwm ntawm Autosomal rigentosa (tus PDP) (ARP), thiab ncua sij hawm rau pde6 muaj nuj nqi thiab ncua sij hawm reginal degelation hauv tsiaj qauv.
Kev Nyuaj Siab thiab Kev Txhim Kho Lub Hlwb: Cov antidepressant muaj peev xwm 'ntawm CGMP
Cov kev tshawb fawb tsis ntev los no tau pom tias qhov tsis txaus ntseeg CGMP piav qhia yog cuam tshuam nrog kev mob hlwb xws li kev nyuaj siab thiab ntxhov siab
Offontex (PFC) Muaj nuj nqi: CGMP hauv PFC tswj glutamatergic Neuron expitability los ntawm PKG. Chronic stress can lead to a decrease in PFC cGMP levels, while PDE5 inhibitors can reverse this change and improve depressive like behavior.
5-ht System System: CGMP tuaj yeem txhim kho 5-HT1a receptor muaj nuj nqi thiab txhawb nqa cov tshuaj tiv thaiv kev tiv thaiv ntawm cov tshuaj tiv thaiv tshuaj tiv thaiv kab mob (xws li SSRIS). Kev sib xyaw ua ke ntawm tadalafil thiab fluoxetine qhia cov tshuaj tiv thaiv kev ywj siab hauv cov tsiaj.
Daim ntawv thov Neuroscience ntawm tadalafil kua tee: kev rau txim kev qhuab qhia los ntawm ed mus rau cns
Cov txiaj ntsig ntawm cov tshuaj: subllingual nqus thiab central nkag mus
Kev tso cai Tsoos Tadalafil yuav tsum tau nqus los ntawm txoj hnyuv plab zom mov thiab raug kev txom nyem los ntawm thawj zaug dhau los thiab ncua sij hawm (30-60 feeb). Cov tee ua kua yog ncaj qha nqus los ntawm kev tshem tawm mucosa thiab muaj cov txiaj ntsig hauv qab no:
Qhov pib nrawm: Deblowual nqus bypasses lub siab metabolism, thiab ntshav tshuaj confinter tau mus txog 15 feeb, haum rau kev cuam tshuam kev sib deev tam sim no (xws li mob siab rau kev sib deev).
Kev Ua Haujlwm Nruab Nrab: Cov kev sim tsiaj tau pom tias muaj kev cuam tshuam ntawm kev tswj hwm cov kua dej yog 2.3
Cov ntaub ntawv thov kho mob nthuav: los ntawm ed mus rau neuroprotection
Raws li ntau lub zog ntawm CGMP hauv lub hlwb, qhov ntsuas tau rauTadalafil kua teemuaj surpassed Ed
Tus ncej kev kho mob stroke: CGMP txhim kho mob stroke raug mob los ntawm kev tshaj tawm Angiogenesis thiab lub siab dua tshiab. Ib theem II sim qhia tias yuav pib siv Tadalafil (5mg / hnub) tsis pub dhau 72 teev tom qab mob stroke tau txhim kho Barthel cov qhab nia ntawm 3 hlis.
Tus kab mob Parkinson (PD): theem ntawm CGMP hauv Dopamininer kev neurons hauv Sucouria Nigra ntawm PD cov neeg mob raug txo qis. Tadalafil yuav ncua tus kab mob los ntawm kev tiv thaiv PDE5 thiab PDE1 (cov tom kawg dhau los ua ntau dua qub hauv Pd).
Kev Raug Mob Siab Lub Hlwb (TBI): CGMP Cov Teebcom Teeb Meem Tom qab TBI cuam tshuam nrog ntev {}} lub sij hawm kev txawj ntse kev nkag siab. Tadalafil tuaj yeem txo cov hippocampal neuronal tuag thiab txhim kho kev nco lub dag zog hauv cov qauv tsiaj.
Kev Nyab Xeeb thiab Ua Haujlwm: Ib qho kev sib tw sib tw hla kev
Txawm hais tias Tadalafil muaj kev nyab xeeb tag nrho, lub chaw haujlwm tseem ceeb yuav tsum them sai sai rau cov teeb meem nram qab no:
Mob taub hau thiab hypotension: CGMP dilation ntawm cov ntshav tseb cov ntshav tuaj yeem ua rau mob taub hau (nrog rau kev siv tshuaj nitrate ua ke tuaj yeem ua rau hypotension.
Pom kev txawv txav: kwv yees li 3% ntawm cov neeg mob cyanosis, uas cuam tshuam nrog tus neeg sib tshuam nrog PDE6 hauv Retina thiab feem ntau yog hloov chaw.
Kev sib cuam tshuam yeeb tshuaj: Tadalafil yog CYP3A4 substrate, thiab thaum siv hauv kev sib xyaw nrog CYP3A4 Modulators xws li Rifampicin thiab Ketoconazole, qhov ntau npaum li cas yuav tsum tau hloov kho.
Yav tom ntej kev coj ua: cov kev cai ncaj ncees ntawm CGMP kev piav qhia thiab kho tus kheej
Xaiv cov tshuaj tiv thaiv kev tiv thaiv PDE subtypes
Tam sim no PDE5 Inhibitors (xws li Tadalafil) Cov khaub ncaws hla ntawm PDE1, PDE6, thiab lwm yam subtypes, uas yuav ua rau cov kev mob tshwm sim. Kev loj hlob ntawm cov nqaij mos -} Tshwj xeeb PDE Insomitors, xws li nanomedicines tsuas yog hippocampal PDE5, yog lub sijhawm yav tom ntej.
CGMP analogues thiab kev kho mob gene
CGMP analogs, xws li 8 {{{- br-cgmp thiab petazocin, tuaj yeem ncaj qha pkgrourration, tab sis cov teeb meem ntawm lub hlwb plotebility thiab kev ruaj khov yuav tsum tau hais.
Kev Kho Mob Gene: Kev cai ntev ntawm CGMP kev piav qhia tuaj yeem ua tiav los ntawm kev xa cov kab mob SGC lossis AVE), thiab kev vam meej ua ntej tau tiav hauv PD Tsiaj qauv.
Kev Tswj Xyuas Cov Kheej Kev Coj Los ntawm Biomarkers
Qeb ntawm CGMP yog cuam tshuam los ntawm noob caj noob ces (xws li PDE5 Gene Polymorchism), hnub nyoog (xws li cov kab mob BBB), thiab cov kab mob BBB Cov tshuaj kho mob tuaj yeem ua tiav los ntawm kev kuaj pom CGMP metabolites (xws li NitroRotyrosine) hauv Cerebrospinal kua lossis ntshav.
Cim npe nrov: Tadalafil Kua tee, lwm tus neeg, chaw tsim khoom, Hoobkas, lag luam wholesale, yuav, nqe, loj, loj, rau muag