I. Kev Taw Qhia
Dermorphin yog ib qho tshwm sim heptapeptide, thawj zaug cais thiab txheeb xyuas thaum xyoo 1970s los ntawm pab pawg kws tshuaj Italian Vittorio Erspamer los ntawm daim tawv nqaij ntawm South American nplooj - npuas qav (Phyllomedusa sauvagei). Nws cov kab ke molecular yog Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH₂. Lub xub ntiag ntawm D-alanine ntawm txoj hauj lwm 2 ua rau muaj kev tiv thaiv zoo rau enzymatic degradation, uas ua rau lub neej ntev dua ib nrab-ntau dua li endogenous opioid peptides.
Tsis zoo li feem ntau ntawm daim tawv nqaij peptides uas ua haujlwm hauv zos xwb, Dermorphin yog ib qho kev xaiv μ-opioid receptor (MOR) agonist. Hauv vitro guinea npua ileum kev sim ua kom pom tias nws cov haujlwm yog kwv yees li 39 npaug ntawm morphine thiab 57 npaug ntawm methionine enkephalin. Nyob rau hauv tus nas spinal dorsal horn nociceptive neuron qauv, nws cov tshuaj muaj zog analgesic raws li kev tswj hwm intrathecal yog kwv yees li 40 npaug ntawm morphine. Cov yam ntxwv ntawm cov tshuaj no txiav txim siab Dermorphin cov xwm txheej tshwj xeeb: nws yog ob qho tib si kev tshawb fawb thiab cov khoom muaj feem cuam tshuam rau kev tsim txom.
Cov hauv qab no suav nrog cov ntaub ntawv tshawb fawb txog kev kho mob / chaw kho mob tau tshaj tawm hauv PubMed thiab cov neeg siv cov lus tawm tswv yim los ntawm cov rooj sib tham hauv zej zog, nthuav tawm ntau daim duab -Dermorphin's tiag tiag - cov ntawv thov hauv ntiaj teb.
II. Cov ntaub ntawv tshawb fawb soj ntsuam: txwv tib neeg cov ntaub ntawv
2.1 Human Spinal Reflex Study (1986)
Sandrini et al. (1986) tau ua thawj txoj kev tshawb fawb txog tib neeg cov teebmeem ntawm Dermorphin hauv cov neeg tuaj yeem noj qab haus huv. Tom qab txhaj tshuaj ntawm 0.16 mg / kg Dermorphin, cov txiaj ntsig hauv qab no tau pom:
Anti-nociceptive effect: Ib qho tseem ceeb, txhawb nqa, thiab zoo- txhais tau tias nce ntxiv ntawm tus txha caj qaum nociceptive flexion reflex qhov pib tau pom, thiab cov txiaj ntsig kuj tau pom nyob rau hauv cov neeg mob uas muaj kev puas tsuaj rau tus txha caj qaum, qhia tias nws qhov chaw tseem ceeb ntawm kev ua yog nyob ntawm tus txha caj qaum.
Ib nrab naloxone thim rov qab: Tsis zoo li morphine thiab enkephalin analogues, uas tuaj yeem tiv thaiv tau los ntawm naloxone, naloxone tsuas yog thim rov qab li ntawm 50% ntawm cov nyhuv Dermorphin, qhia tias nws yuav koom nrog kev cuam tshuam nrog atypical opioid receptors.
koob tshuaj thiab kev nyab xeeb: Kev txhaj tshuaj ntawm 0.16 mg / kg raug zam, thiab tsis muaj qhov tshwm sim tsis zoo tshwm sim.
2.2 Central nervous system teebmeem (tsiaj)
Tartar et al. (1985) pom cov teebmeem ntawm kev tswj hwm intraventricular hauv luav:
EEG hloov: nce tag nrho cortical zog spectral ceev thiab txo hippocampal tag nrho lub zog, raws li tus qauv ntawm μ agonists.
Cov teebmeem autonomic: Ib txhij ua pa nyuaj siab, bradycardia, thiab hypothermia tshwm sim.
Naloxone thim rov qab: 0.5 mg / kg IV naloxone tuaj yeem thim rov qab cov teebmeem saum toj no sai thiab ua tiav.
Gioanni et al. (1991) pom nyob rau hauv nas uas tsis tshua muaj intraventricular koob tshuaj (125 pmol) ntawm Dermorphin tuaj yeem ua rau EEG spikes, myoclonic jerks, thiab qaug dab peg (250-500 pmol), uas tuaj yeem thim rov qab los ntawm naloxone. Qhov no qhia tau hais tias lub qhov rais nqaim heev hauv nruab nrab thiab muaj kev pheej hmoo ua haujlwm tseem ceeb.
III. Cov Lus Qhia Hauv Zej Zog: Kev Paub Txog Tus Neeg Siv
3.1 Lub Zej Zog Loj thiab Cov Ntaub Ntawv Muaj
Dermorphin yuav luag tsis muaj loj - pab pawg neeg siv nyob rau hauv tus kheej - neeg soj ntsuam zej zog. Raws li cov ntaub ntawv los ntawm peptide zej zog cov ntaub ntawv sib sau ua ke platforms, cov peptide no "tsis muaj tus kheej raug cai- neeg soj ntsuam hauv zej zog, lossis ib lub zej zog- cov txheej txheem tsim." Feem ntau ntawm cov kev sib tham yog tsom rau ob peb rooj plaub ntawm lub platforms xws li Reddit, nrog cov ntaub ntawv tsis sib xws thiab tsis sib xws.
3.2 Tus neeg siv kev txhawb siab thiab kev siv cov xwm txheej
Raws li kev txheeb xyuas hauv zej zog, cov neeg siv tau muab faib ua peb pawg:
Kev Tswj Kev Mob: Cov neeg mob uas mob ntev nrhiav lwm txoj hauv kev, xws li cov neeg siv tau ntsib "kev mob txhua hnub theem 8/10 vim muaj paj hlwb."
Kev Txhim Kho Kev Ua Tau Zoo: Qee cov neeg nyiam kev noj qab haus huv tau xav txog nws cov txiaj ntsig ntawm kev txhawb nqa kev loj hlob hormone tso tawm (qhov kev siv no tau txwv los ntawm WADA).
Kev Tshawb Fawb Txog Kev Tshawb Fawb: Qee tus neeg siv tsawg tau sim nws tawm ntawm kev tshawb fawb txaus siab.
3.3 Cov Lus Qhia Txog Cov Neeg Siv Khoom
Dosage Exploration Tsis meej pem
Cov neeg siv Reddit tau tshaj tawm sim koob tshuaj txij li 150 mcg mus rau 1 mg, qee qhov kev tswj hwm subcutaneously:
150-250 mcg: Qee cov neeg siv tau qhia txog kev kho mob ntawm caj dab raug mob ntawm qhov koob tshuaj no.
250-500 mcg: Ib tus neeg siv tau tshaj tawm "tsis muaj qhov sib txawv ntawm qhov xav tau."
1 mg: Lwm tus neeg siv tau tshaj tawm tias "tseem ceeb tab sis tsis muaj kev cuam tshuam tag nrho" nyob rau sab nraub qaum.
Daim ntawv ceeb toom tsis zoo
Kev khaus hnyav: Ib tus neeg siv tau tshaj tawm "qhov khaus khaus tsis tau ntev li peb teev" tom qab txhaj tshuaj 0.5 mg (histamine). (Histamine tso tawm, cov tshuaj tiv thaiv ib txwm)
Kev txhawj xeeb txog kev kam rau siab: Cov neeg siv nrog keeb kwm ntawm kev raug tshuaj opioid xav tias hla - kam rau ua.
Kev pheej hmoo rau kev quav yeeb quav tshuaj: Cov lus ceeb toom tau tshwm sim ntau zaus hauv lub rooj sab laj -"Qhov no yog qhov pib ntawm kev quav yeeb quav tshuaj."
Supply saw thiab ntaub ntawv scarcity
Cov neeg siv feem ntau tshaj tawm tias Dermorphin yog "nyuaj tau, thiab cov ntaub ntawv tshawb fawb ntawm tus kheej tseem tsawg dua." Feem ntau cov kev sib tham revolves nyob ib ncig ntawm cov lus nug: "Nws puas zoo?", "Yuav ua li cas npaum li cas yog txiav txim siab?", "Puas muaj leej twg siv nws?"
3.4 Cov ntaub ntawv tseem ceeb uas ploj lawm
Tsis muaj cov neeg siv hauv zej zog tau tshaj tawm lub hom phiaj sib piv ntawm lub ntsws ua haujlwm ua ntej thiab tom qab kev tswj hwm. Kev nyuaj siab ua pa yog qhov mob hnyav tshaj plaws ntawm μ agonists, tab sis kev sib tham hauv zej zog tsis tshua muaj kev saib xyuas tus kheej ntawm tus kheej ua pa thiab cov ntshav oxygen saturation- qhov tsis muaj nws tus kheej yog qhov muaj kev nyab xeeb loj.
IV. Kev Sib Tham: Txhais Cov Lus Teb Tiag
4.1 A Gap hauv Pov Thawj Zoo
Dermorphin nthuav qhia cov ntaub ntawv tsis tshua muaj:
Abundant in vitro/animal studies (>50, 1979-1990s)
Tsuas yog ib qho kev tshawb fawb soj ntsuam tib neeg (1986, n tsis paub), tsis muaj kev sim tshuaj tom ntej
Kev paub hauv zej zog yog qhov txwv tsis pub tshaj thiab tsis tuaj yeem ntseeg tau, tsis muab cov lus qhia noj ntau npaum li cas
Qhov tseeb tseem ceeb: Dermorphin tau ua tiav qhov kev sim tshuaj rau kev mob tom qab mob / palliative care hauv xyoo 1980s, tab sis kev loj hlob tsis tau tso tseg. Cov kws tshawb fawb tau kwv yees tias txoj kev tswj hwm intrathecal tsis tau cog lus thaum lub sijhawm, thiab qhov kev cia siab tau txais txiaj ntsig tau qis dua li ib txwm μ agonists. Hauv xyoo 2018, cov kws tshawb fawb tau hu rau "rov tshawb pom" ntawm peptide no, tab sis qhov no tseem tsis tau ua tiav.
4.2 Cov Lus Ceeb Toom Txog Kev pheej hmoo -Cov txiaj ntsig zoo
Cov lus thov thoob plaws hauv zej zog tias "Dermorphin tsis muaj tshuaj tiv thaiv tsawg dua li morphine" tsis muaj cov pov thawj zoo -. Qhov tseeb, kev ua kom muaj txiaj ntsig zoo ntawm μ receptors yog inevitably nrog los ntawm kev lom zem ntawm kev ua siab ntev thiab kev vam khom. Raws li ib qho kev sib xyaw nrog lub zog 40 npaug ntawm morphine, qhov kev ua yuam kev ntawm 0.1 mg tuaj yeem ua rau muaj qhov sib txawv ntawm cov tib neeg.
Kev nyuaj siab ua pa, feem ntau ua rau tuag taus ntawm μ agonists, tau lees paub hauv cov tsiaj. Kev txiav txim siab txog kev nyab xeeb hauv zej zog nkaus xwb raws li kev xav ntawm "Kuv nyob zoo" yog qhov tseem ceeb ntxiv kev nyab xeeb ntawm pab pawg los ntawm ib tus neeg muaj hmoo -ib qho kev poob siab loj.
4.3 Sib piv nrog Bronchogen
Piv rau Bronchogen tshuaj xyuas hauv ntu dhau los, Dermorphin sib txawv hauv cov hauv qab no:
Bronchogen: Cov pov thawj tsawg tab sis qis dua (kev tswj hwm qhov ncauj, tsis yog -opioid mechanism)
Dermorphin: Kuj txwv tsis pub muaj pov thawj, tab sis muaj kev pheej hmoo siab heev (muaj zog opioid agonist, kev txhaj tshuaj, ob txoj kev pheej hmoo ntawm kev quav tshuaj thiab kev nyuaj siab ua pa)
V. Xaus
Dermorphin tau ua pov thawj pom tseeb los tiv thaiv -nociceptive nyhuv ntawm tus txha caj qaum hauv cov tib neeg kev tshawb fawb. Nws cov qauv tshwj xeeb, uas ua rau nws muaj kev ruaj ntseg enzyme thiab lub zog siab, ua rau nws yog ib qho kev tshawb fawb tseem ceeb hauv opioid receptor pharmacology. Txawm li cas los xij:
1. Tsis muaj kev pom zoo rau tib neeg daim ntawv thov-Peptide no tsis tau pom zoo los ntawm FDA lossis EMA thiab tam sim no tau muab cais ua cov tshuaj tshawb fawb nruj me ntsis.
2. Tsis muaj koob tshuaj-kev nyab xeeb rau kev siv hauv zej zog-Cov ntaub ntawv ntawm tib neeg txoj hlab ntshav nkaus xwb (0.16 mg/kg) tsis tuaj yeem muab ntxiv rau ntev-lub sij hawm lossis rov siv dua yam tsis muaj kev tshawb fawb txog tshuaj pharmacokinetic thiab kev sib txawv ntawm tus kheej.
3. Qhov txaus ntshai tiag tiag thiab loj heev-Kev nyuaj siab ua pa, qaug dab peg, thiab muaj peev xwm ua rau muaj kev quav yeeb quav tshuaj tau lees paub los ntawm cov ntaub ntawv tsiaj lossis tib neeg.
4. Txoj hauv kev ntawm kev tswj hwm yog qhov tseem ceeb -Intrathecal/ventricular kev tswj hwm muaj zog heev tab sis kuj tseem ceeb heev; peripheral kev tswj hwm (subcutaneous / intravenous) yuav txo tau qee qhov kev pheej hmoo, tab sis lub qhov rais kho mob ntawm cov tshuaj muaj txiaj ntsig thiab tshuaj lom tsis tau ua tiav rau tib neeg.
Rau txhua tus kws tshawb fawb lossis ib tus neeg xav txog kev siv Dermorphin, tsuas yog qhov tsim nyog yog siv nws los ua ib qho kev sim hauv cov tshuaj opioid receptor pharmacology, hauv ib cheeb tsam nrog naloxone cov chaw saib xyuas xwm txheej ceev thiab kev saib xyuas kev tshaj lij, thiab tsis yog rau tus kheej - kev tswj hwm lossis "kev kho mob" lub hom phiaj.