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1kits (Ebipipa 10) .
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▎ PT 141 Enzimba
Ensibuko: PubChem |
Omutendera: Ac-Nle-cyclo(DHFRWK)-OH Ensengekera ya molekyu: C 50H 68N 14O10 Obuzito bwa molekyu: 1025.2g/mol Ennamba ya CAS: 189691-06-3 PubChem CID: 9941379. Omuntu w’abantu Ebigambo ebifaanagana: Bremelanotide |
▎ PT 141 Okunoonyereza
Kiki ekiva mu kunoonyereza ku PT 141?
PT 141 ye synthetic peptide analog era agonist of melanocortin receptors, okusinga omuli MC3R ne MC4R, nga zino zisinga kweyolekera mu central nervous system [1] .Okuzuula PT 141 kuleese essuubi eppya mu kujjanjaba obuzibu mu kwegatta. Okunoonyereza okwasooka ku kyo kwalaga nti okugaba PT 141 ku nvunza n’ebisolo ebiyitibwa primates ebitali bantu kyavaako obusajja okusituka. Oluvannyuma lw’okuweebwa envunza mu nkola, okukola kw’obusimu obuyitibwa neurons mu hypothalamus kwalagibwa okweyongera mu c-Fos immunoreactivity. Obusimu obuyitibwa neurons mu kitundu kye kimu eky’obusimu obw’omu makkati bwanditutte akawuka ka pseudorabies akafukiddwa mu corpus cavernosum y’obusajja bw’envunza [1] .PT 141 erina obusobozi okujjanjaba obutakola bulungi mu kwegatta. Okunoonyereza kulaga nti oluvannyuma lw’okugaba PT 141 eri abasajja aba bulijjo n’abalwadde abalina obuzibu mu kusituka, waaliwo okweyongera okw’amangu era okusinziira ku ddoozi mu kukola kw’okusituka. Ebivudde mu kunoonyereza kuno biraga nti PT 141 erina obusobozi bungi ng’obujjanjabi obupya ku buzibu bw’okwegatta [1]..
Enkola ki PT 141 gy’ekola ku bikwata ku melanocortin?
Enkola entongole PT 141 (Bremelanotide) gy’ekola ku bikwata ku melanocortin esinga kuba nzibu, era bino wammanga bye bikwata ku nkola yaayo mu bujjuvu:
Enkola y’ebikwata melanocortin erimu peptides za melanocortin, ebikwata eby’enjawulo, obutoffaali obuyambi, n’ebiziyiza eby’omunda. Melanocortin peptides ze busimu obutono obuyitibwa peptide hormones obubadde bunoonyezebwa mu mbeera ez’enjawulo ez’omubiri n’endwadde. Mu kiseera kino, waliwo ebika bitaano ebimanyiddwa eby’ebikwata melanocortin, ebibunye mu busimu obw’omu makkati n’ebitundu ebimu eby’okumpi. G protein-coupled melanocortin receptors zitera okutambuza obubonero nga ziyita mu adenylate cyclase n’amakubo amalala agalaga obubonero wansi. Okusinziira ku ligandi, okwolesebwa okw’okungulu kw’ekirungo kya melanocortin, obudde bw’okubeera kw’ekirungo, puloteyina ezikwatagana, ekika ky’obutoffaali, n’ebipimo ebirala, amakubo g’obubonero gazibu era ga pleiotropic. Wadde nga ebitundu byonna ebitaano ebikwata melanocortin biyungibwa ku Gs, oluusi n’oluusi bisobola okuyungibwa ku Gq oba Gi [2]..
Okusiba PT 141 ku bikwata ku melanocortin:
PT 141 ye analog ya peptide. Nga agonist ya melanocortin receptor, esobola okwesiba ku central melanocortin receptors. PT 141, nga synthetic peptide analog of α-melanocyte-stimulating hormone, ye agonist ya melanocortin receptors omuli MC3R ne MC4R, ezisinga okweyolekera mu nkola y’obusimu obw’omu makkati [1]. .
Ebikosa envunza enkazi:
Mu nvunza enkazi, PT 141 elonda okusitula enneeyisa y’omukwano awatali kukosa lordosis, rhythm, oba enneeyisa endala ez’okwegatta. PT 141 tereeta systemic motor activation era tekosa ndowooza ya mpeera z’okwegatta. Kino kiraga nti enkola ya melanocortin ey’omu makkati nkulu mu kulungamya obwagazi bw’abakyala obw’okwegatta. Enkola y’eddagala erongooseddwa ku nneeyisa y’okwegatta ey’okwegomba ey’envunza enkazi temanyiddwangako, era ekifuula PT 141 eyinza okuba eddagala erisoose okuzuulibwa nga lisobola okujjanjaba obuzibu bw’okwegomba kw’abakyala [3]..
Ebikosa envunza n’ebisolo ebitali bantu: Okuweebwa PT 141 ku nvunza n’ebisolo ebitali bantu kivaako obusajja okusituka. Okugaba PT 141 mu nkola kikola obusimu obuyitibwa neurons mu hypothalamus y’envunza, nga kyeyolekera ng’okweyongera mu c-Fos immunoreactivity. Obusimu obuyitibwa neurons mu kitundu kye kimu ekya hypothalamus bujja kutwala akawuka ka pseudorabies akafuyiddwa mu corpus cavernosum y’obusajja bw’envunza [3]..
Ebikosa ebisajja by’abantu:
Okugaba PT 141 eri abasajja aba bulijjo n’abalwadde abalina obuzibu mu kusituka kivaako okweyongera amangu era okusinziira ku ddoozi mu kusituka. Ebivuddemu biraga nti PT 141 esuubirwa okufuuka eddagala eppya erijjanjaba obuzibu mu kwegatta [3]..
Ebikosa abakyala b’abantu: Mu bakyala abasooka okuva mu nsonga abalina obuzibu mu kwegatta, oluvannyuma lw’okuweebwa Bremelanotide mu nnyindo ya ddoozi emu (kwe kugamba, PT 141), abakyala bangi baategeeza nti baalina obwagazi obw’ekigero oba obw’amaanyi. Bw’ogeraageranya ne placebo, waaliwo omuze ogweyoleka ennyo ogw’okuddamu okulungi ku bikwata ku nneewulira z’okuzuukuka kw’ebitundu by’ekyama oluvannyuma lw’okujjanjabwa Bremelanotide. Mu bakyala abaagezaako okwegatta mu ssaawa 24 oluvannyuma lw’okujjanjabwa, abakyala bangi nnyo baali bamativu nnyo n’omutindo gw’okucamuka oluvannyuma lw’okukozesa Bremelanotide bw’ogeraageranya n’eddagala eriweweeza ku bulwadde bwa placebo. Wabula oluvannyuma lw’okuweebwa Bremelanotide, tewaaliwo nkyukakyuka nnene mu kuzimba emisuwa mu bukyala nga balaba obutambi obw’obuseegu [4]..
Mu kumaliriza, nga ekirungo ekiziyiza melanocortin receptor agonist, PT 141, nga yesiba ku melanocortin receptors, ekola ebikolwa eby’enjawulo eby’omubiri mu bikolwa by’ebisolo n’abantu naddala nga kikola kinene mu kulungamya enkola y’okwegatta.
Dose–response effects za PT-141 ku nneeyisa y’okwegatta mu bisenge bya bilevel. (Waggulu) Ebikosa okusaba mu bakazi aba primed ne estrogen ne progesterone (EP) oba estrogen yokka (E yokka). Okugezesebwa okw’oluvannyuma kwalaga nti ddoozi zombi eza 100- ne 200-g/kg zayongera nnyo ku muwendo gw’okusaba bw’ogeraageranya n’abafugibwa abajjanjabiddwa omunnyo (P values <0.05). (Wakati) Ebikosa pacing mu nkazi primed ne EP oba E yokka. (Wansi) Ebikosa ku lordosis quotients mu nkazi primed ne EP oba E yokka. Data zitegeeza SEM. *, P <0.05 okuva mu kufuga.
Ensibuko:PubMed [3] .
Migaso ki egy’enjawulo egisobola okuva mu PT 141 eri abasajja obwagazi obutono n’obuzibu mu kusituka?
Okulongoosa enkola y’okusituka:
Okunoonyereza kungi kulaga nti PT 141 erina ekikolwa ekimu eky’obujjanjabi ku buzibu bw’okusituka kw’abasajja. Okugeza, mu kugezesebwa okumu, kyazuulibwa nti kisobola okuleeta obusajja okusituka [5] (Shadiack AM, 2007). Mu kunoonyereza okwakolebwa mu Phase IIb ku balwadde ba sukaali abasajja abalina obuzibu bw’okusituka, abalwadde bano baalondebwa mu ngeri ey’ekifuulannenge okufuna placebo oba ddoozi ez’enjawulo eza PT 141. Ebivuddemu biraga nti mu bibinja ebyalina ddoozi ezisingako eza PT 141 (12.5mg ne 15mg), waaliwo okulongoosa okw’amaanyi mu kitundu kya Erectile Function (EF) eky’ekitongole kya International Index of Erectile Function (IIEF), nga waliwo enjawulo entegeerekeka bw’ogeraageranya n’ekibinja kya placebo [5]. .
Enkola PT 141 gy’elongoosaamu enkola y’okusituka eyinza okuba nga yeekuusa ku mulimu gwayo ng’eddagala lya melanocortinergic, nga likwatagana n’ebikwata melanocortin mu nkola y’obusimu obw’omu makkati naddala mu hypothalamus. Okusiba kuno kuyinza okulungamya amakubo g’obusimu agakwatagana n’okusituka, bwe kityo ne kitumbula okusituka kw’obusajja [5]. .
Okugumira obulungi n’obukuumi:
Okusinziira ku bumanyirivu mu bujjanjabi bwa Bremelanotide, okugaba eddagala lya melanocortin agonists (nga Bremelanotide) kugumiikiriza bulungi [6] . Tekikwatagana na puleesa ekendedde etunuuliddwa n’eddagala eriziyiza phosphodiesterase-5 eririko kati erikozesebwa mu kujjanjaba obuzibu bw’okusituka.
Okunoonyereza ku bikolwa by’obujjanjabi:
Okwekenenya mu bantu abasajja abalamu n’abalwadde abalina obuzibu mu kusituka:
Oluvannyuma lw’okuweebwa wansi w’olususu mu basajja abalamu n’abalwadde abalina obuzibu bw’okusituka (ED) abaategeeza nti tebaddamu kimala ku Viagra, cyclic heptapeptide melanocortin analog PT 141 yakeberebwa [7] (Rosen RC, 2004). Dozi okuva ku 0.3 okutuuka ku 10 mg zaweebwa abasajja abalamu, era dose ezisukka mu 1.0 mg zavaamu okuddamu okw’okusituka okw’amaanyi mu bibalo. Abalwadde ba ED baafuna placebo, 4 oba 6mg PT 141 mu crossover design nga waliwo visual sexual stimulation (VSS). Ku ddoozi zombi, okuddamu kw’okusituka okwaleetebwa PT 141 kwali kwa maanyi mu bibalo. PT 141 yali terina bulabe era nga egumiikiriza bulungi mu kunoonyereza kwombi. Mu balwadde abatalina kuddamu kumala ku biziyiza PDE5, obusobozi bw’okusituka, okugumiikiriza, n’obusobozi bwa PT 141 okuleeta okusituka okw’amaanyi biraga nti PT 141 eyinza okuwa enkola endala ey’obujjanjabi eri ED eri abalwadde abayinza okuba ab’enjawulo.
Ebiva mu kugatta ne sildenafil:
Abalwadde kkumi na mwenda abalina obuzibu bw’okusituka abeetegeeza nti baddamu Viagra oba Levitra baweebwa 25mg sildenafil ne 7.5mg intranasal PT 141, 25mg sildenafil ne intranasal placebo spray, n’empeke za placebo n’okufuuyira mu nnyindo mu randomized crossover design [8] (Diamond LE, 2005). Okuddamu kw’okusituka ku kusikirizibwa kw’okwegatta okw’okulaba emirundi ebiri okw’eddakiika 30 kwakeberebwa RigiScan. Ebivuddemu biraga nti okuddamu kw’okusituka okwaleetebwa okugatta PT 141 ne sildenafil kwali kunene nnyo okusinga okwaleetebwa sildenafil yokka. Omugatte guno gwali tegulina bulabe era nga gugumiikiriza bulungi, awatali kuleeta bizibu bipya oba okweyongera mu mirundi oba obuzibu bw’ebizibu. Ekimalirizibwa kiri nti okugatta eddagala eriziyiza PT 141 mu nnyindo ne phosphodiesterase 5 liyinza okuwa eky’obujjanjabi eri abalwadde abatakola bulungi oba abalina okugumiikiriza obubi ku ddoozi ezisingako ez’obujjanjabi obw’omu.
Okukozesa PT 141 kwa makulu nnyo mu bintu bingi naddala okuleeta essuubi eppya eri abalwadde bangi mu by’obulamu bw’okwegatta. Ku bakyala nga tebannaba kuva mu nsonga abatawaanyizibwa obulwadde bw’okwegomba okw’okwegatta obufunibwa n’obutakola bulungi (HSDD), PT 141 nkulaakulana nnene. Emabegako, abalwadde ng’abo batera okugumira okunyigirizibwa kw’eby’omwoyo okwava ku bwagazi obutono mu bulamu bwabwe obwa bulijjo, ekyakosa ennyo embeera yaabwe ey’ebirowoozo n’enkolagana ey’oku lusegere ne bannaabwe. Okujja kwa PT 141 kukyusizza embeera eno. Nga etereeza amakubo mu bwongo agakwatibwako mu kuddamu okwegatta, kitereeza nnyo obwagazi bw’abalwadde obw’okwegatta. Ebiwandiiko by’okunoonyereza mu bujjanjabi biraga nti oluvannyuma lw’okukozesa Bremelanotide, waliwo enjawulo eyeeyolese mu nkyukakyuka eza wakati mu Female Sexual Function Index - Desire domain (FSFI-D) n’obubonero bw’ekintu eky’ekkumi n’ettaano mu Female Sexual Distress Scale - Desire/Arousal/Orgasm (FSDS-DAO) okuva ku ntandikwa okutuuka ku nkomerero y’okunoonyereza (EOS).
Kino mu ngeri ey’okutegeera kiraga ebirungi byakyo mu kwongera ku bwagazi bw’abalwadde mu kwegatta n’okukendeeza ku buzibu obukwatagana nabyo, okutumbula ennyo omutindo gw’obulamu bw’abakyala abalina HSDD nga tebannagenda mu nsonga n’okubayamba okuddamu okwekkiririzaamu n’essanyu ly’obulamu.
Ekirala, PT 141 era eraga ebirungi ebiyinza okuvaamu ku butakola bulungi mu kwegatta kw’abasajja. Mu nsonga y’okulongoosa obwagazi bw’abasajja obw’okwegatta obutono, abalwadde bangi baategeeza nti kweyongera nnyo oluvannyuma lw’okukikozesa, ne basobola okuddamu okwagala okwegatta. Era ku bikwata ku buzibu bw’okusituka, enkola y’okusituka kw’abalwadde abamu erongooseddwa okutuuka ku ddaala eritali limu oluvannyuma lw’okubakozesa, ne kyongera ku buzibu bw’okusituka kw’obusajja, ne kibasobozesa okumaliriza enneeyisa y’okwegatta obulungi mu bulamu bw’okwegatta n’okulongoosa obumanyirivu bwabwe mu kwegatta.
Kino awatali kubuusabuusa kimalawo omugugu gw’omubiri n’obwongo eri ekibinja ky’abasajja ekibadde kitawaanyizibwa obutakola bulungi mu by’okwegatta okumala ebbanga eddene, kiddaabiriza obuvune mu birowoozo obuva ku buzibu bw’enkola y’okwegatta, era kiyamba n’okukuuma enkolagana n’obutebenkevu bw’enkolagana y’amaka.
Okusinziira ku ndowooza ya macroscopic ey’okunoonyereza ku by’obusawo, okukozesa PT 141 kuwa obujulizi obw’omugaso obw’omugaso okunoonyereza okw’obwegendereza ku nkola ezikwata ku bulamu bw’omuntu obw’okwegatta.
Enkola y’okunoonyereza ku nkola yaayo ey’okukola ereetedde abanoonyereza okukola okunoonyereza okw’obwegendereza okusingawo ku makubo g’obusimu mu bwongo agakwatagana n’okuddamu kw’okwegatta, ebikwata melanocortin, n’ebirala, okutumbula enkulaakulana y’okunoonyereza okusookerwako mu by’obulamu bw’okwegatta, okuteekawo omusingi gw’okukola enkola endala ez’obujjanjabi n’eddagala eriwonya obutakola bulungi mu kwegatta, okwongera okugaggawaza eggwanika ly’obusawo, n’okukwata eddaala erinywevu mu maaso olw’eddagala mu kuvvuunuka okusoomoozebwa kw’ebizibu by’obulamu bw’okwegatta.
Ebikwata ku Muwandiisi
Ebintu ebyogeddwako waggulu byonna binoonyerezeddwako, birongooseddwa era ne bikung’aanyizibwa kkampuni ya Cocer Peptides.
Omuwandiisi wa Scientific Journal Pfaus JG omuyivu ow’ekitiibwa akwatagana n’amatendekero ag’ekitiibwa agawerako, omuli Charles University Prague, Czech National Institute of Mental Health, Universidad Veracruzana, Concordia University mu Canada, Rockefeller University, ne University of British Columbia. Okunoonyereza kwe kukwata ku misomo mingi, okusinga kussa essira ku Sayansi w’Enneeyisa, Neurosciences & Neurology, Psychology, Endocrinology & Metabolism, ne Urology & Nephrology.
Mu kitundu kya Sayansi w’Enneeyisa, Pfaus anoonyereza ku nneeyisa enzibu n’enkola zazo ezisibukako. Omulimu gwe mu Neurosciences & Neurology gugenda mu maaso n’ensengeka n’enkola y’obusimu, ne guyamba okutegeera obuzibu bw’obusimu n’enkola z’okutegeera. Mu Psychology, okunoonyereza kwe kuyinza okwekenneenya enkola z’enneeyisa n’enkola z’ebirowoozo, nga kuwa amagezi ku nneeyisa y’abantu n’obulamu bw’obwongo. Mu Endocrinology & Metabolism, anoonyereza ku nkola z’obusimu n’enkola z’enkyukakyuka mu mubiri, ebiyinza okuyunga emirimu gino egy’ebiramu n’enneeyisa. Omulimu gwe mu Urology & Nephrology guyinza okussa essira ku nsonga z’omubiri n’endwadde z’enkola y’omusulo n’ensigo, nga kiyinzika okunoonyereza ku ngeri enkola zino gye zikwataganamu n’emirimu n’enneeyisa endala ez’omubiri.
Mu myaka gye gyonna, James G. Pfaus kirabika afulumizza empapula nnyingi era n’ayamba nnyo mu kibiina kya ssaayansi, n’aziba ebituli wakati w’ebitundu bya ssaayansi eby’enjawulo n’okutumbula okunoonyereza okuva mu bitongole ebitali bimu. Omulimu gwe tegukoma ku kutumbula kutegeera kwa ndowooza ku misomo gino naye era gulina ebigendererwa eby’omugaso ku by’obulamu n’okukulaakulanya enkola z’obujjanjabi. Pfaus JG ewandiikiddwa mu kiwandiiko ekijuliziddwa [3].
