Ipa 10 mg

▎ Ipa Structure

Source: PubChem

Sequence: XHXFK Molecular Formula: C 38H 49N 9O5 Molecular Luj: 711.9 g / mol CAS Nr .: 170851-70-4 PubChem CID: 9831659 Synonyms: NNC-26-0161; UNII-Y9M3S784Z6; Ipa ACETATE

▎ Ipa Tshawb Fawb

Kev tshawb fawb keeb kwm ntawm Ipa yog dab tsi?

Kev ua paug plab qeeb yog ib qho mob tshwm sim, thiab tam sim no, muaj ob peb txoj kev kho mob zoo. Kev tshawb fawb pom tau tias Ipa, raws li ib tug hluavtaws peptidomimetic, ua rau ghrelin receptor thiab tej zaum yuav muaj ib tug kho nyhuv ntawm qeeb plab hnyuv. Hauv kev tshawb fawb ntawm tus nas qauv ntawm gastroparesis, gastroparesis raug ntxias los ntawm kev phais plab thiab plab hnyuv, thiab nws tau pom tias Ipa tuaj yeem ua rau lub plab zom mov ^[1].

Postoperative ileus yog ib qho kev sib tw tseem ceeb hauv kev kho mob, tsis muaj cov tswv yim tswj xyuas zoo. Ghrelin receptor stimulation muaj kev txhawb nqa kev txhawb nqa ntawm ob qho tib si sab sauv thiab sab hauv ntawm txoj hnyuv. Raws li ghrelin receptor agonist, Ipa muaj peev xwm siv tau tus nqi hauv kev kho mob tom qab ileus. Piv txwv li, nyob rau hauv ib txoj kev tshawb no, ib tug yav tom ntej, randomized, tswj pov thawj-ntawm-lub tswv yim txoj kev tshawb no tau ua nyob rau hauv cov neeg mob nyob rau hauv lub plab hnyuv resection tom qab phais plab los soj ntsuam kev nyab xeeb thiab kev ua tau zoo ntawm Ipa ^[2].

Ipa belongs rau txoj kev loj hlob hormone tso tawm peptides (GHRPs), uas yog ib tug hluavtaws pentapeptide muaj peev xwm txhawb kev tso tawm ntawm kev loj hlob hormone los ntawm lub hypothalamus thiab pituitary caj pas. Kev loj hlob hormone plays lub luag haujlwm tseem ceeb hauv lub cev kev loj hlob, kho, thiab metabolism, yog li lub luag haujlwm ntawm Ipa hauv kev tswj hwm kev loj hlob hormone kuj tau txais kev saib xyuas thoob plaws ^[3].

Vim nws muaj peev xwm muaj txiaj ntsig hauv kev kho mob qeeb hauv plab hnyuv, postoperative ileus, thiab nws lub luag haujlwm raws li kev loj hlob hormone tso tawm peptide, Ipa tau nyiam kev tshawb fawb ntau.

Lub mechanism ntawm kev txiav txim ntawm Ipa yog dab tsi?

1. Stimulating tso tawm ntawm kev loj hlob hormone: 

Ipa belongs rau kev loj hlob hormone tso tawm peptides (GHRPs), uas tuaj yeem txhawb kev tso tawm cov tshuaj hormones loj hlob los ntawm hypothalamus thiab pituitary caj pas. Hauv vitro thiab hauv vivo kev sim, Ipa tau pom tias muaj zog thiab muaj txiaj ntsig hauv kev tso tawm cov tshuaj hormones loj hlob. Piv txwv li, nyob rau hauv ib txoj kev tshawb no, lub hwj chim thiab kev ua tau zoo ntawm Ipa nyob rau hauv tso kev loj hlob hormone los ntawm cov thawj nas pituitary hlwb zoo ib yam li cov GHRP-6 ^[3] . Nws cov txheej txheem ntawm kev ua haujlwm yog los txhawb kev tso tawm ntawm kev loj hlob hormone los ntawm kev ua kom GHRP zoo li receptors. Los ntawm kev tshuaj xyuas tshuaj, nws tau raug lees paub tias zoo li GHRP-6, Ipa txhawb kev tso tawm ntawm kev loj hlob hormone los ntawm GHRP-zoo li receptors.

2. Kev cuam tshuam rau lub plab zom mov

Accelerating plab hnyuv plab: 

Hauv cov qauv nas, Ipa tuaj yeem ua kom lub plab zom mov. Kev phais plab ua rau lub plab zom mov qeeb, tab sis tom qab kev tswj hwm ntawm Ipa (0.014 µmol / kg intravenously), lub plab khoob tau nrawm dua. Ipa stimulates gastric contractility thiab ua kom lub plab khoob los ntawm kev sib kho los ntawm kev ua kom cov ghrelin receptor, koom nrog cholinergic excitatory neurons (Greenwood-Van Meerveld B, 2012).

Txhim kho cov tsos mob ntawm postoperative ileus: 

Hauv cov qauv nas ntawm postoperative ileus, Ipa tuaj yeem txhim kho cov tsos mob. Tom qab kev tswj hwm ntawm Ipa tom qab, ib koob tshuaj Ipa (1mg / kg) lossis GHRP-6 (20μg / kg) tuaj yeem txo lub sijhawm rau thawj zaug tso quav. Rov ua dua kev tswj hwm ntawm Ipa (0.1 lossis 1mg / kg) tuaj yeem ua rau muaj txiaj ntsig ntau ntxiv, noj zaub mov, thiab qhov hnyav nce ^[4].

3. Kev cuam tshuam rau kev tso tawm insulin

Ipa tuaj yeem tsim cov tshuaj insulin tso rau hauv cov ntaub so ntswg ntawm cov nqaij mos ntawm cov nas thiab cov kab mob ntshav qab zib. Kev nce hauv insulin secretion tshwm sim los ntawm Ipa tuaj yeem cuam tshuam los ntawm diltiazem, yohimbine, propranolol, lossis kev sib xyaw ntawm atropine, propranolol, thiab yohimbine. Hauv cov nas mob ntshav qab zib, atropine tuaj yeem txo qis cov insulin tso tawm los ntawm Ipa, tab sis qhov kev cuam tshuam no tsis pom hauv cov nas ib txwm muaj. Qhov no qhia tau tias Ipa txhawb kev tso tawm insulin los ntawm calcium channel thiab adrenergic receptor txoj hauv kev ^[5].

4. Txo qhov mob

Hauv kev sim ua qauv ntawm non-inflammatory visceral hypersensitivity thiab somatic mechanical allodynia, Ipa, raws li ib qho peripheral txwv ghrelin receptor agonist, tuaj yeem txo qis colonic hypersensitivity thiab somatic allodynia. Nws cov txheej txheem ntawm kev txiav txim yog kho los ntawm ghrelin receptor, thiab cov nyhuv antinociceptive tuaj yeem thaiv los ntawm ghrelin receptor antagonist H0900 ^[6].

S yuav ua li cas cov txiaj ntsig ntawm Ipa ntawm insulin tso tawm los ntawm cov kab mob pancreatic tawg ntawm cov nas ib txwm muaj thiab mob ntshav qab zib.

Source: PubMed ^[5]

Cov ntawv thov Ipa yog dab tsi?

1. Txhawb kev tso tawm ntawm kev loj hlob hormone

Ipa tuaj yeem txhawb kev tso tawm ntawm kev loj hlob hormone los ntawm hypothalamus thiab pituitary caj pas. Kev loj hlob hormone plays lub luag haujlwm tseem ceeb hauv tib neeg lub cev, suav nrog kev txhawb nqa cov protein synthesis, cell proliferation, thiab kho cov ntaub so ntswg. Yog li, Ipa tuaj yeem siv los kho kev loj hlob hormone tsis txaus lossis lwm yam kab mob ntsig txog kev loj hlob hormone tsis txaus ^[7].

2. Txhim kho txoj hnyuv ua haujlwm

Accelerating plab hnyuv plab: 

Hauv cov qauv nas, Ipa ua kom lub plab zom mov hauv cov qauv ntawm postoperative ileus los ntawm ib qho kev sib kho los ntawm kev ua kom lub cev loj hlob tso tawm peptide receptor, koom nrog cholinergic excitatory neurons ^[1] . Kev phais plab ua rau lub plab zom mov qeeb, thiab kev tswj hwm ntawm Ipa tuaj yeem txo qhov feem ntawm cov zaub mov seem hauv plab, yog li txhim kho plab hnyuv.

 Txhawb nqa plab hnyuv peristalsis: 

Hauv cov qauv nas ntawm postoperative ileus, Ipa tuaj yeem txhim kho cov tsos mob ntawm cov neeg mob. Piv txwv li, nyob rau hauv tus qauv nas, Ipa tuaj yeem txo lub sij hawm rau thawj qhov quav tom qab phais, ua kom cov zis tso zis ntau ntxiv, noj zaub mov, thiab qhov hnyav nce ^[4] . Rov ua dua kev tswj hwm ntawm Ipa tuaj yeem ua rau muaj txiaj ntsig ntau ntxiv, kev noj zaub mov kom tsawg, thiab qhov hnyav nce, qhia txog nws cov txiaj ntsig zoo rau kev ua haujlwm ntawm plab hnyuv.

3. Kho qhov mob

Relieving visceral thiab somatic mob: 

Kev tshawb fawb qhia tau hais tias Ipa, raws li kev loj hlob hormone tso tawm peptide receptor agonist, muaj antinociceptive zog. Hauv kev sim ua qauv yam tsis muaj colonic epithelial o, Ipa tuaj yeem txo qhov tsis muaj qhov tsis zoo ntawm lub qhov muag pom kev thiab somatic mechanical allodynia ^[6].

Nws cov txheej txheem ntawm kev ua haujlwm tuaj yeem kho los ntawm kev loj hlob hormone tso tawm peptide receptor, koom nrog kev tswj hwm ntawm visceral thiab somatic hypersensitivity, muab txoj hauv kev tshiab rau kev kho mob visceral thiab somatic mob.

Dab tsi yog qhov kev tshawb fawb ntawm Ipa hauv kev kho mob ntawm kev loj hlob hormone deficiency?

Kev loj hlob hormone deficiency yog ib yam kab mob uas tshwm sim los ntawm tsis txaus tso tawm ntawm kev loj hlob hormone los ntawm anterior pituitary caj pas, uas yuav cuam tshuam rau kev loj hlob thiab kev loj hlob ntawm cov me nyuam thiab lub cev metabolism ntawm cov neeg laus. Nyob rau hauv xyoo tsis ntev los no, Ipa, raws li ib tug loj hlob hormone secretagogue, tau nyiam thoob plaws hauv kev kho mob ntawm kev loj hlob hormone deficiency. Cov hauv qab no yog cov kev tshawb fawb txog kev nce qib ntawm Ipa hauv kev kho mob ntawm kev loj hlob hormone deficiency.

1. Cov nyhuv stimulating ntawm Ipa ntawm kev loj hlob hormone secretion

Ipa tuaj yeem txhawb kev tso tawm ntawm kev loj hlob hormone. Kev tshawb fawb qhia tau hais tias Ipa tuaj yeem ua ke nrog kev loj hlob hormone tso tawm hormone (GHRH) los txhim kho kev tso tawm ntawm kev loj hlob hormone ^[8] . Hauv kev sim tsiaj, tom qab 21 hnub ntawm kev kho mob ntev nrog Ipa hauv cov poj niam hluas nas, piv nrog cov pab pawg tswj hwm, qhov kev loj hlob hormone tso tawm hauv monolayer kab lis kev cai ntawm pituitary hlwb nce. Tib lub sijhawm, Ipa thiab GHRH tuaj yeem txhawb kev tso tawm cov tshuaj hormones loj hlob los ntawm cov kab mob pituitary hauv vitro. Txawm li cas los xij, hauv pawg GHRH pretreatment, qhov kev loj hlob ntawm cov tshuaj hormones tom ntej rau kev txhawb nqa tsis tau txhim kho, thaum nyob hauv pawg Ipa pretreatment, tsis muaj qhov tshwm sim desensitization, qhia tias Ipa tsis ua rau desensitization ntawm kev loj hlob hormone teb nyob rau hauv cov poj niam nas ^[8].

2. Cov nyhuv ntawm Ipa rau qhov hnyav nce

Kev tswj hwm ntev ntawm Ipa tuaj yeem ua kom qhov hnyav ntawm cov poj niam hluas nas. Kev saib xyuas txhua hnub qhia tau hais tias feem pua ​​​​ntawm qhov hnyav nce hauv Ipa pretreatment pab pawg thiab GHRH pretreatment pawg yog siab dua li hauv pawg tswj hwm ^[8] . Qhov no muaj feem xyuam rau qhov tseeb tias Ipa stimulates secretion ntawm kev loj hlob hormone, uas nyob rau hauv lem txhawb cov protein synthesis thiab cell loj hlob.

3. Cov nyhuv ntawm Ipa ntawm kev tsim cov pob txha

Hauv cov qauv nas laus, nws tau pom tias qhov kev loj hlob hormone secretagogue Ipa tuaj yeem tiv thaiv cov teebmeem catabolic ntawm glucocorticoids (GC) ntawm cov leeg pob txha thiab pob txha. Piv nrog rau cov pab pawg txhaj nrog GC ib leeg, nyob rau hauv cov tsiaj txhaj nrog GC thiab Ipa, qhov siab tshaj plaws tetanic nro ntawm cov leeg nqaij nyuj nce ntxiv, thiab cov pob txha periosteal tsim tau nce plaub npaug ^{[8, 9]} . Qhov no qhia tau hais tias Ipa muaj txiaj ntsig zoo rau kev tswj cov leeg nqaij thiab txhawb kev tsim cov pob txha, thiab tuaj yeem pab tiv thaiv cov teeb meem xws li pob txha pob txha hauv cov neeg mob uas tsis muaj kev loj hlob hormone.

4. Cov nyhuv ntawm Ipa ntawm kev ua haujlwm ntawm plab hnyuv

Raws li kev xaiv kev loj hlob hormone-tso cov tshuaj hormone agonist thiab kev loj hlob hormone-tso peptide receptor agonist, Ipa tau qhia txog kev kho mob zoo hauv tus nas qauv ntawm kev mob plab hnyuv tuag tes tuag taw. Kev tswj hwm ib leeg ntawm Ipa lossis kev loj hlob hormone-tso peptide (GHRP)-6 txo lub sijhawm rau thawj zaug tom qab lub plab zom mov, tab sis tsis muaj kev cuam tshuam rau kev tso zis ntau ntxiv, noj zaub mov, lossis qhov hnyav nce. Ipa tsub kom fecal tso zis ntau, noj zaub mov, thiab hnyav nce. Qhov no qhia tias Ipa yuav muaj qee lub luag haujlwm hauv kev txhim kho plab hnyuv thiab tuaj yeem pab txhim kho kev zom zaub mov thiab nqus dej hauv cov neeg mob uas tsis muaj kev loj hlob hormone. ^[4].

Hauv cov ntsiab lus, raws li kev xaiv kev loj hlob hormone secretion txhawb nqa, Ipa ua tau zoo txhawb kev tso tawm ntawm kev loj hlob hormone los ntawm kev ua kom muaj kev loj hlob hormone-tso peptide receptor (GHS receptor), tsis muaj kev cuam tshuam rau qib ntawm adrenocorticotropic hormone (ACTH) thiab cortisol. Nws cov haujlwm muaj xws li txhawb kev loj hlob hormone secretion, tswj lub plab hnyuv motility, thiab alleviating mob. Nws cov kev xaiv siab thiab cov yam ntxwv ntau lub hom phiaj pom zoo rau kev siv tshuaj kho mob muaj peev xwm, ua rau nws tsim nyog siv rau hauv cov xwm txheej xws li kev loj hlob hormone deficiency, postoperative plab hnyuv obstruction, thiab kev tswj mob.

Hais Txog Tus Sau

Cov ntaub ntawv hais saum toj no yog txhua yam tshawb fawb, kho thiab sau los ntawm Cocer Peptides.

Scientific Journal Author

Raun K yog tus kws tshawb fawb koom nrog Technical University of Denmark (DTU) thiab Novo Nordisk Foundation. Nws txoj kev tshawb fawb nyiam nthuav dav ntau yam kev qhuab qhia, suav nrog Endocrinology & Metabolism, Orthopedics, Nutrition & Dietetics, Veterinary Sciences, thiab Engineering. Nws txoj haujlwm feem ntau tsom mus rau kev txhim kho cov kev daws teeb meem zoo thiab tsim kho tshiab, tshwj xeeb hauv cov ntsiab lus ntawm biotechnology thiab bio-based kev lag luam.

Raun K tau pab txhawb rau cov haujlwm uas cuam tshuam nrog Novo Nordisk Foundation Center rau Biosustainability ntawm DTU, uas tau mob siab rau kev tsim kho cell Hoobkas tsim, metabolic engineering, thiab hluavtaws biology rau sustainable bioproduction. Tsis tas li ntawd, nws tau koom nrog hauv kev tshawb fawb pib los txo qis kev cia siab ntawm cov ntaub ntawv fossil thiab txhawb kev hloov pauv ntsuab los ntawm kev daws teeb meem bioproduction.

Nws txoj haujlwm tseem cuam tshuam txog kev siv engineering, xws li kev tsim cov catalysts thiab bioprocesses rau kev lag luam thiab ib puag ncig kev ruaj ntseg. Raun K txoj kev sib txuas lus txuas txuas txuas rau kev tshawb fawb thiab kev siv tswv yim, ua rau muaj txiaj ntsig zoo rau kev kawm thiab kev lag luam. Raun K tau teev nyob rau hauv qhov kev siv ntawm cov ntaub ntawv pov thawj [3].

▎ Cov Lus Qhia Tseem Ceeb

[1] Greenwood-Van Meerveld B, Tyler K, Mohammadi E, Pietra C. Kev ua tau zoo ntawm Ipa, ghrelin mimetic, ntawm plab dysmotility nyob rau hauv tus nas qauv ntawm postoperative ileus. Phau ntawv Journal ntawm kev sim tshuaj 2012; 4: 149-55.DOI:10.2147/JEP.S35396.

[2] Beck DE, Sweeney WB, McCarter MD. Cov yav tom ntej, randomized, tswj, pov thawj-ntawm-lub tswv yim kawm ntawm Ghrelin mimetic Ipa rau kev tswj hwm ntawm postoperative ileus hauv cov neeg mob plab hnyuv. INT J COLORECTAL DIS 2014; 29(12): 1527-34.DOI:10.1007/s00384-014-2030-8.

[3] Raun K, Hansen BS, Johansen NL, et al. Ipa, thawj qhov kev loj hlob hormone secretagogue. EUR J ENDOCRINOL 1998; 139(5): 552-61.DOI:10.1530/eje.0.1390552.

[4] Venkova K, Mann W, Nelson R, Greenwood-Van Meerveld B. Efficacy of Ipa, a Novel Ghrelin Mimetic, in a Rodent Model of Postoperative Ileus. J PHARMACOL EXP THER 2009; 329(3): 1110-6.DOI:10.1124/jpet.108.149211.

[5] Adeghate EA, Ponery AS. Mechanism ntawm Ipa-evoked insulin tso tawm los ntawm txiav txiav ntawm cov nas ib txwm thiab ntshav qab zib. Neuro endocrinology ntawv 2004; 256:403-6.

[6] N Mohammadi E, Louwies T, Pietra C, Northrup SR, Greenwood-Van Meerveld B. Attenuation of Visceral and Somatic Nociception by Ghrelin Mimetics. J Exp Pharmacol 2020; 12: 267-74.DOI: 10.2147/JEP.S249747.

[7] Papak M. Ipa - struktur thiab funkcija.; 2016.

https://www.semanticscholar.org/paper/IpastrukturaifunkcijaPapak/6f1496dcedd60ec60a90be4c1f317a8bad7efb08

[8] Jiménez-Reina L, Cañete R, de la Torre MJ, Bernal G. Kev cuam tshuam ntawm kev kho mob ntev nrog kev loj hlob hormone secretagogue Ipa, hauv cov poj niam hluas nas:: somatotroph teb hauv vitro. HISTOL HISTOPATHOL 2002; 17(3): 707-14. PIB: 10.14670/HH-17.707

[9] Andersen NB, F KMO, Johansen PB, Andreassen TT, Rtoft GO, Oxlund H. Txoj kev loj hlob hormone secretagogue Ipa counteracts glucocorticoid-induced txo cov pob txha tsim ntawm cov laus nas. Kev loj hlob hormone & IGF kev tshawb fawb : official journal ntawm Growth Hormone Research Society thiab International IGF Research Society 2001; 11 5: 266-72.DOI:10.1054/GHIR.2001.0239.

Tag nrho cov kab lus thiab cov ntaub ntawv ntawm cov khoom lag luam muab rau ntawm lub vev xaib no tsuas yog rau cov ntaub ntawv tshaj tawm kev tshaj tawm thiab cov hom phiaj kev kawm.  

Cov khoom muab rau hauv lub vev xaib no yog npaj tshwj xeeb rau kev tshawb fawb hauv vitro. Kev tshawb fawb hauv vitro (Latin: * hauv iav *, lub ntsiab lus hauv iav) yog ua los ntawm tib neeg lub cev. Cov khoom no tsis yog tshuaj, tsis tau txais kev pom zoo los ntawm US Food and Drug Administration (FDA), thiab yuav tsum tsis txhob siv los tiv thaiv, kho, lossis kho txhua yam mob, kab mob, lossis mob. Nws raug txwv nruj raws li txoj cai los qhia cov khoom no rau hauv tib neeg lossis tsiaj lub cev hauv txhua daim ntawv.