Tidak ada mekanisme kerja rasetam yang diterima secara universal. Rasetam secara umum menunjukkan afinitas yang dapat diabaikan untuk reseptorsistem saraf pusat yang umum, tetapi modulasi neurotransmiter pusat termasuk asetilkolina dan glutamat telah dilaporkan. Meskipun anirasetam dan nebrasetam menunjukkan beberapa afinitas untuk reseptor asetilkolin muskarinik, hanya nefirasetam yang menunjukkan interaksi nanomolar dengan reseptor neurotransmiter. Modifikasi mekanisme transduksi sinyal pusat yang terletak di membran merupakan hipotesis lain.[3]
Seperti beberapa ampakine, beberapa rasetam seperti pirasetam dan anirasetam merupakan modulator alosterik positif dari reseptor AMPA.[7]
Rasetam dipahami bekerja dengan memodulasi reseptor glutamat secara alosterik, khususnya reseptor AMPA, yang menyebabkan masuknya Ca2+ yang bersifat eksitatori.[8] Rasetam dianggap dapat meningkatkan daya ingat melalui interaksi dengan reseptor glutamat di sistem saraf pusat.
Fenilpirasetam, yang unik di antara rasetam karena merupakan fenetilamina dan stimulan, merupakan penghambat penyerapan kembali dopamin atipikal.[9][10][11][12]
Rasetam antikonvulsan termasuk levetirasetam, brivarasetam, dan seletrasetam bertindak sebagai ligan glikoprotein vesikel sinaptik 2A (SV2A).[6] Analog yang lebih baru dari agen-agen ini, yakni padsevonil, bukan lagi rasetam itu sendiri tetapi jauh lebih kuat dibandingkan dan berinteraksi tidak hanya dengan SV2A tetapi juga glikoprotein vesikel sinaptik 2B (SV2B) dan glikoprotein vesikel sinaptik 2C (SV2C).[6]
Metilfenilpirasetam, turunan fenilpirasetam, merupakan modulator alosterik positif dari reseptor sigma σ1.[10][13][14][15] Saat ini ia adalah satu-satunya rasetam yang diketahui memiliki aksi ini.[10]
Kofaktor
Dalam penelitian dengan tikus tua, peningkatan yang nyata telah diamati dalam tugas kognitif pada kelompok eksperimen yang diberi pirasetam. Kinerja semakin meningkat ketika pirasetam dikombinasikan dengan kolin. Bukti dalam penelitian dengan tikus menunjukkan bahwa potensi pirasetam meningkat ketika diberikan dengan kolin.[16]
Rasetam adalah turunan 2-pirolidon dan terkadang disebut hanya sebagai pirolidon (2-oksopirolidina).[1] Kebanyakan memiliki inti 2-okso-1-pirolidinaasetamida, yang merupakan struktur kimia pirasetam.
Beberapa agen yang termasuk dalam keluarga rasetam secara teknis bukan rasetam sendiri dalam hal struktur kimia dan sebaliknya merupakan senyawa yang terkait erat.[17] Mereka dapat disebut sebagai "mirip rasetam".[2][17] Agen-agen ini termasuk alorasetam, molrasetam, omberasetam, padsevonil, dan tenilsetam.[6][17][18]
Masyarakat dan budaya
Legalitas
Australia
Semua rasetam termasuk zat yang termasuk dalam jadwal 4 di Australia berdasarkan Standar Racun (Februari 2020). Zat yang termasuk dalam jadwal 4 diklasifikasikan sebagai "Obat yang Hanya Dapat Diresepkan, atau Obat Hewan yang Dapat Diresepkan – Zat yang penggunaan atau penyediaannya harus oleh atau atas perintah orang yang diizinkan oleh undang-undang Negara Bagian atau Wilayah untuk meresepkan dan harus tersedia dari apoteker dengan resep."[19]
^ abcdMalykh AG, Sadaie MR (February 2010). "Piracetam and piracetam-like drugs: from basic science to novel clinical applications to CNS disorders". Drugs. 70 (3): 287–312. doi:10.2165/11319230-000000000-00000. PMID20166767.
^ abcGualtieri F, Manetti D, Romanelli MN, Ghelardini C (2002). "Design and study of piracetam-like nootropics, controversial members of the problematic class of cognition-enhancing drugs". Current Pharmaceutical Design. 8 (2): 125–138. doi:10.2174/1381612023396582. PMID11812254.
^ abGouliaev AH, Senning A (May 1994). "Piracetam and other structurally related nootropics". Brain Res Brain Res Rev. 19 (2): 180–222. doi:10.1016/0165-0173(94)90011-6. PMID8061686.
^Copani A, Genazzani AA, Aleppo G, Casabona G, Canonico PL, Scapagnini U, Nicoletti F (April 1992). "Nootropic drugs positively modulate alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-sensitive glutamate receptors in neuronal cultures". Journal of Neurochemistry. 58 (4): 1199–204. doi:10.1111/j.1471-4159.1992.tb11329.x. PMID1372342.
^Molina-Carballo A, Checa-Ros A, Muñoz-Hoyos A (July 2016). "Treatments and compositions for attention deficit hyperactivity disorder: a patent review". Expert Opin Ther Pat. 26 (7): 799–814. doi:10.1080/13543776.2016.1182989. PMID27138211. The racetams have different activities [e.g., phenylpiracetam is a stimulant developed and marketed in Russia, piracetam is a nootropic, and levetiracetam is widely used as an anticonvulsant (Figure 17)].
^ abcVeinberg G, Vavers E, Orlova N, Kuznecovs J, Domracheva I, Vorona M, Zvejniece L, Dambrova M (2015). "Stereochemistry of phenylpiracetam and its methyl derivative: improvement of the pharmacological profile". Chemistry of Heterocyclic Compounds. 51 (7): 601–606. doi:10.1007/s10593-015-1747-9. ISSN0009-3122. Phenylpiracetam was originally designed as a nootropic drug for the sustenance and improvement of the physical condition and cognition abilities of Soviet space crews.2 Later, especially during the last decade, phenylpiracetam was introduced into general clinical practice in Russia and in some Eastern European countries. The possible target receptors and mechanisms for the acute activity of this drug remained unclear, until very recently it was found that (R)-phenylpiracetam (5) (MRZ-9547) is a selective dopamine transporter inhibitor that moderately stimulates striatal dopamine release.19
^Sommer S, Danysz W, Russ H, Valastro B, Flik G, Hauber W (December 2014). "The dopamine reuptake inhibitor MRZ-9547 increases progressive ratio responding in rats". The International Journal of Neuropsychopharmacology. 17 (12): 2045–2056. doi:10.1017/S1461145714000996. PMID24964269. Here, we tested the effects of MRZ-9547 [...], and its l-enantiomer MRZ-9546 on effort-related decision making in rats. The racemic form of these compounds referred to as phenotropil has been shown to stimulate motor activity in rats (Zvejniece et al., 2011) and enhance physical capacity and cognition in humans (Malykh and Sadaie, 2010). [...] MRZ-9547 turned out to be a DAT inhibitor as shown by displacement of binding of [125I] RTI-55 (IC50 = 4.82 ± 0.05 μM, n=3) to human recombinant DAT expressed in CHO-K1 cells and inhibition of DA uptake (IC50 = 14.5 ± 1.6 μM, n=2) in functional assays in the same cells. It inhibited norepinephrine transporter (NET) with an IC50 of 182 μM (one experiment in duplicate). The potencies for the l-enantiomer MRZ-9546 were as follows: DAT binding (Ki = 34.8 ± 14.8 μM, n=3), DAT function (IC50 = 65.5 ± 8.3 μM, n=2) and NET function (IC50 = 667 μM, one experiment performed in duplicate).
^Stutz PV, Golani LK, Witkin JM (February 2019). "Animal models of fatigue in major depressive disorder". Physiology & Behavior. 199: 300–305. doi:10.1016/j.physbeh.2018.11.042. PMID30513290. In a study performed by Sommer et al. (2014), healthy rats treated with the selective dopamine transport (DAT) inhibitor MRZ-9547 (Fig. 1) chose high effort, high reward more often than their untreated matched controls. Unlike similar studies, however, depressive symptoms were not induced before treatment; rather, baseline healthy controls were compared to healthy rats treated with MRZ-9547. [...] In one study, the selective DAT inhibitor MRZ-9547 increased the number of lever presses more than untreated controls (Sommer et al., 2014). The investigators concluded that such effort-based “decision making in rodents could provide an animal model for motivational dysfunctions related to effort expenditure such as fatigue, e.g. in Parkinson's disease or major depression.” Based upon the findings with MRZ-9547, they suggested that this drug mechanism might be a valuable therapeutic entity for fatigue in neurological and neuropsychiatric disorders. [...] A high effort bias been reported with bupropion (Randall et al., 2015), lisdexamfetamine (Yohn etal., 2016e), and the DA uptake blockers MRZ-9547 (Sommer et al., 2014), PRX-14040 (Fig. 1) (Yohn et al., 2016d) and GBR12909 (Fig. 1) (Yohn et al., 2016c).
^Bartus RT, Dean RL, Sherman KA, Friedman E, Beer B (1981). "Profound effects of combining choline and piracetam on memory enhancement and cholinergic function in aged rats". Neurobiology of Aging. 2 (2): 105–11. doi:10.1016/0197-4580(81)90007-5. PMID7301036.
^ abc"Classification Status of Racetams"(PDF). Medsafe. 2015. Diakses tanggal 1 October 2024. Many of the products are based on a group of compounds known collectively as racetams or 'racetam-like' substances. [...] In addition, three substances that do not strictly meet the racetam definition (due to lack of a 2-pyrrolidone ring) are typically described as being part of the racetam family. These are aloracetam, molracetam and noopept.
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