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1kits （10Ibikoresho）
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▎ PT 141 Imiterere
Inkomoko: PubChem |
Urukurikirane: Ac-Nle-cyclo (DHFRWK) -OH Inzira ya molekulari: C 50H 68N 14O.10 Uburemere bwa molekuline: 1025.2g / mol Numero ya CAS: 189691-06-3 CIDCID CID: 9941379 Synonyme: Bremelanotide |
PT 141 Ubushakashatsi
Ni ubuhe bushakashatsi bwakozwe muri PT 141?
PT 141 ni igereranya rya peptide ya peptide hamwe na agonist ya reseptor ya melanocortine, cyane cyane harimo MC3R na MC4R, bigaragara cyane muri sisitemu yo hagati yo hagati [1] .Ivumburwa rya PT 141 ryazanye ibyiringiro bishya byo kuvura imikorere mibi yimibonano mpuzabitsina. Ubushakashatsi bwambere kuri bwo bwerekanye ko guha PT 141 imbeba na primates zitari abantu byatumye habaho igitsina. Nyuma yubuyobozi bwa sisitemu ku mbeba, imikorere ya neuron muri hypothalamus yerekanwe no kwiyongera kwa immunoreactivite c-Fos. Neuron mu karere kamwe ka sisitemu yo hagati yo hagati yafata virusi ya pseudorabies yatewe muri corpus cavernosum yimboro yimbeba [1] .PT 141 ifite ubushobozi bwo kuvura imikorere mibi yimibonano mpuzabitsina. Ubushakashatsi bwerekanye ko nyuma yo gutanga PT 141 kubagabo basanzwe n’abarwayi bafite imikorere mibi y’umugabo, habayeho kwiyongera byihuse kandi biterwa nigipimo cyibikorwa byigitsina. Ibisubizo byerekana ko PT 141 ifite amahirwe menshi nkumuti mushya wo gukora nabi imibonano mpuzabitsina [1].
Nubuhe buryo PT 141 ikora kuri reseptor ya melanocortine?
Uburyo bwihariye PT 141 (Bremelanotide) ikora kuri reseptor ya melanocortine iragoye, kandi ibikurikira nuburyo burambuye kuburyo bwabwo:
Sisitemu ya reseptor ya melanocortin igizwe na peptide ya melanocortine, reseptor idasanzwe, proteyine zikoreshwa, hamwe na antogenous antagonist. Pelanide ya Melanocortin ni imisemburo mito ya peptide yakozwe mu bihe bitandukanye bya physiologique na patologi. Kugeza ubu, hari ubwoko butanu buzwi bwa reseptor ya melanocortine, ikwirakwizwa muri sisitemu yo hagati yo hagati hamwe nuduce tumwe na tumwe. G proteine ihujwe na melanocortin yakira mubisanzwe itanga ibimenyetso binyuze muri adenylate cyclase nizindi nzira zerekana inzira. Ukurikije ligand, imiterere yubuso bwa reseptor ya melanocortine, igihe cyo kwakira reseptor, poroteyine zijyanye, ubwoko bwakagari, nibindi bipimo, inzira yerekana inzira iragoye kandi ya pleiotropique. Nubwo reseptor ya melanocortine uko ari itanu ihujwe na Gs, irashobora rimwe na rimwe no guhuzwa na Gq cyangwa Gi [2].
Guhambira PT 141 kubakira melanocortin:
PT 141 nikigereranyo cya peptide. Nka melanocortin reseptor agonist, irashobora guhuza na reseptor ya melanocortine. PT 141, nka peptide ya peptide igereranya imisemburo itera α-melanocyte, ni agoniste ya melanocortine yakira harimo MC3R na MC4R, bigaragarira cyane cyane muri sisitemu yo hagati [1] .
Ingaruka ku mbeba z'abagore:
Imbeba z’abagore, PT 141 itoranya guhitamo imyitwarire yo kurambagizanya itagize ingaruka kuri nyagasani, injyana, cyangwa indi myitwarire yimibonano mpuzabitsina. PT 141 ntabwo itera moteri ikora kandi ntabwo igira ingaruka kumyumvire yigihembo cyimibonano mpuzabitsina. Ibi byerekana ko sisitemu ya melanocortine yo hagati ari ngombwa muguhuza irari ry'abagore. Ingaruka za farumasi zatoranijwe ku myitwarire yimibonano mpuzabitsina yimbeba z’abagore ntizigeze zivugwa mbere, ibyo bikaba bituma PT 141 ishobora kuba imiti ya mbere yamenyekanye ishobora kuvura indwara zishingiye ku gitsina cy’abagore [3].
Ingaruka ku mbeba na primates zitari abantu: Ubuyobozi bwa PT 141 kuri imbeba na primates zidafite abantu zitera igitsina. Imiyoborere itunganijwe ya PT 141 ikora neuron muri hypothalamus yimbeba, igaragara nkubwiyongere bwa immunoreactivite c-Fos. Neuron mu karere kamwe ka hypothalamus izafata virusi ya pseudorabies yatewe muri corpus cavernosum yimboro yimbeba [3].
Ingaruka ku bagabo b'abantu:
Ubuyobozi bwa PT 141 kubagabo basanzwe nabarwayi bafite imikorere mibi yumugabo itera kwiyongera byihuse kandi biterwa nigikorwa cyibikorwa byubugingo. Ibisubizo byerekana ko PT 141 iteganijwe kuba uburyo bushya bwo kuvura imikorere mibi yimibonano mpuzabitsina [3].
Ingaruka ku gitsina gore cyabantu: Mu bagore batwite bafite ikibazo cyo gukangura imibonano mpuzabitsina, nyuma yubuyobozi bumwe bwa intranasal ya Bremelanotide (ni ukuvuga PT 141), abagore benshi bavuze ko bafite ubushake buke cyangwa bukabije bwo guhuza ibitsina. Ugereranije na placebo, hari inzira yagaragaye yibisubizo byiza bijyanye n'amarangamutima yo kubyutsa igitsina nyuma yo kuvurwa kwa Bremelanotide. Mu bagore bagerageje gukora imibonano mpuzabitsina mu masaha 24 nyuma yo kuvurwa, ku buryo bugaragara abagore benshi banyuzwe n’urwego rwo kubyutsa igitsina nyuma yo gukoresha Bremelanotide ugereranije na placebo. Icyakora, nyuma yubutegetsi bwa Bremelanotide, nta mpinduka nini yagaragaye muri vasocongestion ibyara igihe ureba amashusho yerekana porunogarafiya [4].
Mu gusoza, nka melanocortin reseptor agonist, PT 141, muguhuza reseptor ya melanocortine, itanga ingaruka zitandukanye mumiterere yinyamanswa yabantu ndetse nabantu, cyane cyane igira uruhare runini mugutunganya imikorere yimibonano mpuzabitsina.
Dose - ibisubizo bya PT-141 kumyitwarire yimibonano mpuzabitsina mubyumba bya bilevel. . Ibizamini bya post hoc byagaragaje ko dosiye ya 100- na 200-g / kg yongereye umubare wabasabye ugereranije nigenzura ryakozwe na saline (P agaciro ＜ 0.05). (Hagati) Ingaruka zo kwihuta kubagore byerekanwe na EP cyangwa E wenyine. . Amakuru ni SEM. *, P ＜ 0.05 uhereye kugenzura.
Inkomoko: Byatangajwe [3]
Ni izihe nyungu zishobora guterwa na PT 141 kubushake buke bwimibonano mpuzabitsina nabagabo bafite ibibazo?
Gutezimbere imikorere yubugingo:
Ubushakashatsi bwinshi bwerekanye ko PT 141 igira ingaruka zimwe zo kuvura imikorere mibi yumugabo. Kurugero, mubigeragezo bimwe na bimwe byamavuriro, wasangaga bishobora gutera igitsina [5] (Shadiack AM, 2007). Mu cyiciro cya IIb cy’abarwayi ba diyabete y’abagabo bafite ikibazo cyo kudakora neza, abarwayi bahawe amahirwe yo kwakira umwanya wa dosiye cyangwa dosiye zitandukanye za PT 141. Ibisubizo byerekanye ko mu matsinda afite dosiye nyinshi za PT 141 (12.5mg na 15mg), habaye iterambere ryinshi mu mikorere ya Erectile (EF) y’urwego mpuzamahanga rw’ibikorwa bya Erectile (IIEF), hamwe n’ahantu hasobanutse [IIEF); .
Uburyo PT 141 itezimbere imikorere yumugabo irashobora kuba ifitanye isano ninshingano zayo nkumuti wa melanocortinergique, uhuza reseptor ya melanocortine muri sisitemu yo hagati yo hagati, cyane cyane muri hypothalamus. Uku guhambira gushobora kugenga inzira zifatika zijyanye no kwubaka, bityo bigatera imbere igitsina . .
Kwihanganirana neza n'umutekano:
Dukurikije uburambe bw’ubuvuzi bwa Bremelanotide, ubuyobozi bwa melanocortin agoniste (nka Bremelanotide) bwihanganirwa neza [6] . Ntabwo ifitanye isano na hypotension yagaragaye hamwe na fosiforiesterase-5 inhibitor ikoreshwa mukuvura imikorere mibi.
Inyigisho zishingiye ku mavuriro:
Isuzumabumenyi mu bagabo bafite ubuzima bwiza n’abarwayi bafite imikorere mibi:
Nyuma yubuyobozi bwubutaka bwibintu byubuzima bwiza bwabagabo n’abarwayi bafite imikorere mibi (ED) batangaje ko igisubizo kidahagije kuri Viagra, hasuzumwe cyclica heptapeptide melanocortin analog PT 141 ( Rosen RC, 2004). Dose iri hagati ya 0.3 na 10 mg yatanzwe kubagabo bafite ubuzima buzira umuze, kandi dosiye irenga 1.0 mg yatanze ibisubizo bifatika byerekana imibare. Abarwayi ba ED bakiriye umwanya, 4 cyangwa 6mg PT 141 mugushushanya kwambukiranya imibonano mpuzabitsina (VSS). Kuri dosiye zombi, igisubizo cya erectile cyatewe na PT 141 cyari gifite imibare ikomeye. PT 141 yari ifite umutekano kandi yihanganirwa neza muri ubwo bushakashatsi bwombi. Ku barwayi badafite igisubizo gihagije kuri PDE5 inhibitor, ubushobozi bwo guhagarara, kwihanganira, hamwe nubushobozi bwa PT 141 bwo gutera intambwe igaragara byerekana ko PT 141 ishobora gutanga ubundi buryo bwo kuvura ED kubarwayi benshi bashobora kuba.
Ingaruka zo guhuza hamwe na sildenafil:
Abarwayi 19 badafite imikorere mibi ya erekile bavuze ubwabo ko basubije Viagra cyangwa Levitra bahawe 25mg sildenafil na 7.5mg intranasal PT 141, 25mg sildenafil hamwe na spran ya perezidansi, hamwe na tableto ya platbo hamwe na spran ya spranike muburyo bwateganijwe bwambukiranya imipaka [8] (Diamond LE, 2005). Igisubizo cya erectile kubintu bibiri byiminota 30 yimibonano mpuzabitsina byasuzumwe na RigiScan. Ibisubizo byerekanaga ko igisubizo cya erectile cyatewe no guhuza PT 141 na sildenafil cyari kinini cyane kuruta icyatewe na sildenafil wenyine. Gukomatanya byari bifite umutekano kandi byihanganirwa, nta gutera ibintu bishya bibi cyangwa kwiyongera inshuro cyangwa ubukana bwibintu bibi. Umwanzuro nuko guhuza intranasal PT 141 na phosphodiesterase 5 inhibitor bishobora gutanga uburyo bwo kuvura abarwayi badakora neza cyangwa bafite kwihanganira nabi kurwego rwo hejuru rwa monotherapy.
Gukoresha PT 141 bifite akamaro kanini mubice byinshi, cyane cyane kuzana ibyiringiro bishya kubarwayi benshi mubijyanye nubuzima bwimibonano mpuzabitsina. Ku bagore batwite barwaye indwara ya hypoactive yifuza cyane (HSDD), PT 141 ni intambwe ikomeye. Mbere, abarwayi nkabo bakunze kwihanganira igitutu cyimitekerereze iterwa nubushake buke bwimibonano mpuzabitsina mubuzima bwabo bwa buri munsi, ibyo bikaba byaragize ingaruka zikomeye kumarangamutima yabo no mubucuti bwa hafi nabagenzi babo. Kugaragara kwa PT 141 byahinduye iki kibazo. Mugutunganya inzira mubwonko bugira uruhare mubisubizo byimibonano mpuzabitsina, bitezimbere cyane ubushake bwimibonano mpuzabitsina bwabarwayi. Ubushakashatsi bw’ubuvuzi bwerekana ko nyuma yo gukoresha Bremelanotide, hari itandukaniro rigaragara mu mpinduka zigereranijwe zerekana imikorere y’imibonano mpuzabitsina y’Abagore - Icyifuzo cya domeni (FSFI-D) hamwe n’amanota ya 13 y’amanota y’ibitsina by’umugore - Icyifuzo / Arousal / Orgasm (FSDS-DAO) kuva ku murongo fatizo kugeza ku iherezo ry’ubushakashatsi (EOS).
Ibi byerekana neza ingaruka nziza zabyo mukuzamura ibyifuzo byabarwayi no kugabanya imibabaro ifitanye isano, kuzamura imibereho yabategarugori batwite bafite HSDD no kubafasha kugarura ikizere numunezero wubuzima.
Byongeye kandi, PT 141 irerekana kandi ingaruka nziza zishobora gukora kumikorere mibi yumugabo. Mu rwego rwo kunoza ubushake buke bw’igitsina gabo, abarwayi benshi bavuze ko kwiyongera gukomeye nyuma yo kuyikoresha, bashoboye kugarura inyungu zabo mu mibonano mpuzabitsina. Naho kubyerekeye ingorane zifatika, imikorere yabarwayi bamwe na bamwe yahinduwe neza mugihe runaka nyuma yo kuyikoresha, byongera ingaruka zo gutera igitsina, bibafasha kurangiza imyitwarire yimibonano mpuzabitsina neza mubuzima bwimibonano mpuzabitsina no kunoza uburambe bwabo.
Nta gushidikanya ko byorohereza umutwaro wumubiri nubwenge kumatsinda yabagabo umaze igihe kinini uhangayikishijwe nubusambanyi bukabije, ugasana ihungabana ryimitekerereze yatewe nibibazo byimikorere yimibonano mpuzabitsina, kandi bikanafasha gukomeza ubwuzuzanye n’umutekano byimibanire yumuryango.
Duhereye kuri macroscopique yubushakashatsi bwubuvuzi, gukoresha PT 141 bitanga ibimenyetso bifatika byubushakashatsi bwimbitse bwuburyo bujyanye nubuzima bwimibonano mpuzabitsina.
Gahunda yubushakashatsi bwibikorwa byayo yatumye abashakashatsi bakora ubushakashatsi bwimbitse bwinzira zubwonko mu bwonko bujyanye nigisubizo cyimibonano mpuzabitsina, reseptor ya melanocortin, nibindi, biteza imbere iterambere ryubushakashatsi bwibanze mubijyanye nubuzima bwimibonano mpuzabitsina, hashyirwaho urufatiro rwiterambere ryuburyo bwinshi bwo kuvura nibiyobyabwenge byangiza imikorere mibi yimibonano mpuzabitsina, no gutera intambwe ishimishije kubibazo byubuzima bikemura ibibazo byubuzima.
Ibyerekeye Umwanditsi
Ibikoresho byavuzwe haruguru byose byakorewe ubushakashatsi, byahinduwe kandi byakozwe na Cocer Peptides.
Umwanditsi w'ikinyamakuru Scientific Pfaus JG wize amasomo ajyanye n’ibigo byinshi bizwi, birimo kaminuza ya Charles Prague, Ikigo cy’igihugu gishinzwe ubuzima bwo mu mutwe cya Tchèque, Universidad Veracruzana, kaminuza ya Concordia muri Kanada, kaminuza ya Rockefeller, na kaminuza ya Columbiya y’Ubwongereza. Ubushakashatsi bwe bwibanze ku bumenyi butandukanye, cyane cyane bwibanze ku bumenyi bw'imyitwarire, Neurosciences & Neurology, Psychology, Endocrinology & Metabolism, na Urology & Nephrology.
Mu rwego rwa siyanse yimyitwarire, Pfaus akora ubushakashatsi bwimyitwarire igoye hamwe nuburyo bukoreshwa. Ibikorwa bye muri Neurosciences & Neurology byinjira mu miterere n'imikorere ya sisitemu y'imitsi, bigira uruhare mu gusobanukirwa n'indwara zifata ubwonko n'inzira zo kumenya. Muri psychologiya, ubushakashatsi bwe bushobora gusuzuma imiterere yimyitwarire nuburyo bwo mumutwe, bigatanga ubumenyi bwimyitwarire yumuntu nubuzima bwo mumutwe. Muri Endocrinology & Metabolism, akora iperereza kuri sisitemu ya hormone hamwe na metabolike, birashoboka guhuza iyi mikorere yibinyabuzima nimyitwarire. Ibikorwa bye muri Urology & Nephrology bishobora kwibanda kumiterere ya physiologique na patologique ya sisitemu yinkari nimpyiko, birashoboka ko yashakisha uburyo ubwo buryo bukorana nindi mirimo yumubiri nimyitwarire.
Mu mibereho ye yose, James G. Pfaus ashobora kuba yarasohoye impapuro nyinshi kandi akagira uruhare runini mu bumenyi bwa siyansi, agakemura icyuho kiri hagati y’ubumenyi butandukanye ndetse anateza imbere ubushakashatsi butandukanye. Igikorwa cye nticyateza imbere imyumvire yizi nyigisho gusa ahubwo gifite n'ingaruka zifatika mubuvuzi no guteza imbere ibikorwa byo kuvura. Pfaus JG yanditse kurutonde rwerekana [3].
