Sunifiram (DM235) foda (314728-85-3)

Sunifiram (DM-235) foda an san shi azaman AMPAkine saboda aiwatar da mafi yawan ayyukansa ta hanyar mai karɓar AMPA (ɗayan manyan abubuwan uku na masu karɓar glutamate, kusa da NDMA da kainate). Wannan haɓaka aikin AMPA da alama yana dogaro ne akan haɓakar siginar ta hanyar glycine mai ɗaukar nauyin masu karɓa na NMDA, kodayake alamar ƙarancin alama ta ratsa mai karɓar NMDA sannan fa'idodin masu karɓar AMPA kamar suna dogaro ne.

Sunifiram (DM-235) foda shine kayan aikin bincike na gwaji da aka samo daga Piperazine wanda ke da tasirin anti-amnesia. Ana haɗuwa dashi sau da yawa tare da abubuwan racetam amma a zahiri ba racetam ba ne saboda kasusuwa na pyrrolidone na karya.

Binciken dabbobi ya nuna cewa tana da babban iko fiye da Piracetam ko Phenylpiracetam. Sunifiram yana da alaƙa da Unifiram - sigar sauƙaƙe ce ta Unifram. Nazarin dabbobi sun nuna cewa yanayin maɓalli ɗaya na aiki don Sunifiram shine ta hanyar hulɗa tare da tsarin glutamergic - musamman ta kunnawa AMPA-receptor. Saboda haka ana ɗaukar shi AMPAkine.

A cikin 2006, masu bincike sun nuna cewa Sunifiram da Unifiram sun kasance umarni huɗu na girman girma fiye da Piracetam. Kodayake abubuwan haɗin gwiwar basu nuna kusanci ga mahimman shafuka masu mahimmanci ba, an samo su don hana amnesia ta hanyar daidaituwa na tsarin neurotransmitter daban-daban da kuma ta hanyar haɓakar acetylcholine a cikin cortex na cerebral.

Sunifiram yana haɓaka alamar NMDA mai dogaro da siginar ta hanyar ƙara yawan PKCα phosphorylation, a kewayon sashi na 10-100nM. Wannan hanyar aiwatar da aiki ya dogara da kasancewar shafin ɗaurin glycine kuma an nuna Sunifiram a matsayin mai adawa da glycine a taro na 300μM.

Bugu da ƙari, ƙarin aikin kunnawa mai karɓar AMPA yana da alaƙa da haɓaka aikin CAMKII da PKCα phosphorylation. Kodayake binciken ya tabbatar da cewa sunadaran intracellular kamar CAMKII da PKCα ana kunna su bayan gudanarwar Sunifiram, sauran sunadarai kamar CaMKIV da ERK ba su da illa.

Briefarin taƙaitaccen tsarin aikin, kamar yadda ake fahimta a yanzu, shine cewa Sunifiram yana aiki akan shafin ɗaukar nauyin glycine mai karɓa na NMDA, wanda ke haifar da ƙara siginar alama da kunna ƙwayoyin CAMKII da PKCα da ingantaccen tsari mai kyau na masu karɓar AMPA.

Babu nazarin toxicology da aka gudanar ta amfani da batutuwan ɗan adam.

Studyaya daga cikin binciken ya gano cewa mafi ƙarancin amfani ga Sunifiram ya kasance kamar 0.001mg / kg, kuma marubutan sun gaza samun sakamako masu guba, koda a sigogi 1000-ninka mafi girma (1mg / kg). Binciken da aka lura da inganci na sunifiram (0.001mg / kg wanda aka nuna mafi ƙarancin amfani) ya kasa gano alamun cutar mai guba tare da allurar girma mafi girma 1000 (1mg / kg).

Karatun dabbobi:

Nazarin dabbobi sun nuna cewa Sunifiram yana da ikon haɓaka ƙarfin aiki na tsawon lokaci (LTP) ta ingantaccen aiki. A cikin binciken vivo, a cikin adadin sashi na 0.01-1mg / kg don kwanaki 7-12, nuna cewa tasirin Sunifiram ya dogara ne da farko a kan glycine mai ɗaukar hoto a masu karɓar NMDA kuma daga baya ya kara yawan masu karɓar AMPA. [6] studiesarin nazarin dabbobi sun nuna cewa sashi na 1mg / kg yana da ikon hana rage ƙwaƙwalwar ajiya bayan lokacin horo a cikin jiji tare da raunin ƙwaƙwalwar ƙwayar hippocampal. Bugu da kari, Sunifiram ya sami damar inganta iya daukar lokaci mai tsawo a cikin wadannan dabbobi.

Bincike ya nuna cewa duka Unifiram da Sunifiram (wadanda ke da alaƙa da AMPAkines) suna da damar iya rage amnesia wanda AMB mai karɓar amsar NBQX (30mg / kg ip), a gwajin karɓar linzamin kwamfuta. Abubuwan Nootropic ba su lalata daidaiton motsi ba, motility, ko aikin dubawa. Bugu da ƙari, duka mahaɗin sun juyar da ƙiyayya na kynurenic acid a cikin NMDA-mai sulhu [3 (H) H] NA saki a cikin sarewar hippocampal.

Sunifram har yanzu yana da ƙwaƙƙwaran ƙwaƙwalwar gwaji kuma har yanzu ba a fuskantar da shi ba a kowane gwaji na asibiti na mutum ko karatun toxicology. Saboda haka yana da mahimmanci a lura da yiwuwar haɗarin yanayin wannan fili ga ƙwararrun ƙwararrun masu bincike. Ba a yarda da Sunifiram don siyar da magunguna a kowace ƙasa ba.

Bugu da ƙari, binciken dabbobi ya nuna cewa sashi na 0.01mg / kg yana ƙaruwa da sakin acetylcholine zuwa 200% a cikin sa'a guda na allura, a cikin cortex bera prefrontal. Ba a ganin wannan tasiri a mafi girman sashi na 1mg / kg.

COA

• Romanelli M, Galeotti N, Ghelardini C, Manetti D, Martini E, Gualtieri F. (2006). Tsarin ilimin Pharmacological na DM232 (unifiram) da DM235 (sunifiram), sabon haɓaka ƙarfin haɓaka. Sanarwa da Magungunan CNS, 12 (1): 39-52.
• Moriguchi S, Tanaka T, Narahashi T, Fukunaga K. (2013). Sunifiram na nootropic na noveropic yana haɓaka aikin maganin ecpocampal synaptik ta hanyar glycine mai ɗaukar hoto na mai karɓar N-methyl-D-aspartate. Hippocampus, 23 (10): 942-51.
• Moriguchi S, Tanaka T, Tagashira H, Narahashi T, Fukunaga K. (2013) Novel nootropic miyagun ƙwayoyi sunifiram yana inganta haɓakar haɓaka ta hanyar CaM kinase II da furotin kinase C kunnawa a cikin ƙwaƙwalwar ƙwaƙwalwar ƙwaƙwalwar ƙwaƙwalwa. Behav Brain Res, 242: 150-7.
• Manetti D, Ghelardini C, Bartolini A, Dei S, Galeotti N, Gualtieri F, Romanelli MN, Teodori E. (2000) Sauƙaƙan kwayoyin halitta na 1,4-diazabicyclo {4.3.0} wadanda ba-9-ba suna ba da kayan piperazine waɗanda ke kiyayewa babban aikin nootropic. J Med Chem, 43 (23): 4499-507.
• Galeotti N, Ghelardini C, Pittaluga A, Pugliese AM, Bartolini A, Manetti D, Romanelli MN, Gualtieri F. (2003). AMPA-receptor kunnawa yana cikin tasirin antiamnesic na DM232 (unifiram) da DM235 (sunifiram). Naunyn Schmiedeberg's Arch Pharmacol, 368: 538-545.
• Ghelardini C, Galeotti N, Gualtieri F, Romanelli MN, Bucherelli C, Baldi E, Bartolini A. (2002). DM235 (Sunifiram): Littafin nootropic labari ne wanda ke da haɓaka azaman mai haɓaka hankali. Naunyn-Schmiedeberg's Arch Pharmacol, 365: 419-426.
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