Rilmazafone[1] (リスミー, Rhythmy, previously known as 450191-S) is a water-soluble prodrug developed in Japan.[2] Once metabolized, rilmazafone is converted into several benzodiazepine metabolites that have sedative and hypnotic effects.[3][4] These metabolites induce impairment of motor function and have hypnotic properties.[5]
Rilmazafone is not a benzodiazepine, since there is no benzene ring fused with a diazepine ring in the compound; in fact, the parent drug has no diazepine ring. It is therefore not classified as a benzodiazepine in several countries, including the United States, where it is not designated a controlled substance. Rilmazafone has no effects on benzodiazepine receptors itself, nor does it produce any psychoactive effects prior to metabolism. However, once inside the body it is metabolized by aminopeptidase enzymes in the small intestine to form the principal active benzodiazepine 8-chloro-6-(2-chlorophenyl)-N,N-dimethyl-4H-1,2,4-triazolo [1,5-a][1,4]benzodiazepine-2-carboxamide.[6][7] As can be seen in the molecular diagram below, the principal metabolite contains a benzodiazepine ring structure (i.e., a benzene ring fused with a diazepine ring), unlike the parent compound (rilmazafone), which has no diazepine ring.
^Yamamoto K, Hirose K, Matsushita A, Yoshimura K, Sawada T, Eigyo M, Jyoyama H, Fujita A, Matsubara K, Tsukinoki Y (July 1984). "[Pharmacological studies of a new sleep-inducer, 1H-1,2,4-triazolyl benzophenone derivatives (450191-S) (I). Behavioral analysis]". Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica (in Japanese). 84 (1): 109–54. doi:10.1254/fpj.84.109. PMID 6149174.
^Yamamoto K, Matsushita A, Sawada T, Naito Y, Yoshimura K, Takesue H, Utsumi S, Kawasaki K, Hirono S, Koshida H (July 1984). "[Pharmacology of a new sleep inducer, 1H-1,2,4-triazolyl benzophenone derivative, 450191-S (II). Sleep-inducing activity and effect on the motor system]". Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica (in Japanese). 84 (1): 25–89. doi:10.1254/fpj.84.25. PMID 6149175.
^Ibii N, Horiuchi M, Yamamoto K (August 1984). "[Pharmacology of a 1H-1, 2, 4-triazolyl benzophenone derivative (450191-S), a new sleep-inducer (III). Behavioral study on interactions of 450191-S and other drugs in mice]". Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica (in Japanese). 84 (2): 155–73. doi:10.1254/fpj.84.155. PMID 6149177.
^Yasui M, Kato A, Kanemasa T, Murata S, Nishitomi K, Koike K, et al. (June 2005). "[Pharmacological profiles of benzodiazepinergic hypnotics and correlations with receptor subtypes]". Nihon Shinkei Seishin Yakurigaku Zasshi = Japanese Journal of Psychopharmacology. 25 (3): 143–51. PMID 16045197.
^Koike M, Norikura R, Sugeno K (March 1986). "Intestinal activation of a new sleep inducer 450191-S, a 1H-1,2,4-triazolyl benzophenone derivative, in rats". Journal of Pharmacobio-Dynamics. 9 (3): 315–20. doi:10.1248/bpb1978.9.315. PMID 3454653.
^Muranushi N, Miyauchi S, Suzuki H, Sugiyama Y, Hanano M, Kinoshita H, Oguma T, Yamada H (May 1993). "Comparative hepatic transport of desglycylated and cyclic metabolites of rilmazafone in rats: analysis by multiple indicator dilution method". Biopharmaceutics & Drug Disposition. 14 (4): 279–90. doi:10.1002/bdd.2510140402. PMID 8499579. S2CID 24923818.
rilmazafone, リスミー, rhythmy, previously, known, 450191, water, soluble, prodrug, developed, japan, once, metabolized, rilmazafone, converted, into, several, benzodiazepine, metabolites, that, have, sedative, hypnotic, effects, these, metabolites, induce, impair. Rilmazafone 1 リスミー Rhythmy previously known as 450191 S is a water soluble prodrug developed in Japan 2 Once metabolized rilmazafone is converted into several benzodiazepine metabolites that have sedative and hypnotic effects 3 4 These metabolites induce impairment of motor function and have hypnotic properties 5 RilmazafoneClinical dataTrade namesRhythmyOther names5 2 aminoacetyl amino methyl 1 4 chloro 2 2 chlorobenzoyl phenyl N N dimethyl 1 2 4 triazole 3 carboxamideAHFS Drugs comInternational Drug NamesRoutes ofadministrationOral tablets ATC codenoneLegal statusLegal statusUS OTC Uncontrolled Rx only JP Pharmacokinetic dataElimination half life10 5 hExcretionUrineIdentifiersIUPAC name 1 4 chloro 2 2 chlorobenzoyl phenyl 5 glycylamino methyl N N dimethyl 1H 1 2 4 triazole 3 carboxamideCAS Number99593 25 6 YPubChem CID5069ChemSpider4891 YUNIICU3H37T766KEGGD08481 YCompTox Dashboard EPA DTXSID10244150Chemical and physical dataFormulaC 21H 20Cl 2N 6O 3Molar mass475 33 g mol 13D model JSmol Interactive imageSMILES ClC1 C C C2 CC Cl CC C2N3C CNC CN O NC C N C C O N3 O C CC C1InChI InChI 1S C21H20Cl2N6O3 c1 28 2 21 32 20 26 17 11 25 18 30 10 24 29 27 20 16 8 7 12 22 9 14 16 19 31 13 5 3 4 6 15 13 23 h3 9H 10 11 24H2 1 2H3 H 25 30 YKey KYHFRCPLIGODFH UHFFFAOYSA N Y verify Rilmazafone is not a benzodiazepine since there is no benzene ring fused with a diazepine ring in the compound in fact the parent drug has no diazepine ring It is therefore not classified as a benzodiazepine in several countries including the United States where it is not designated a controlled substance Rilmazafone has no effects on benzodiazepine receptors itself nor does it produce any psychoactive effects prior to metabolism However once inside the body it is metabolized by aminopeptidase enzymes in the small intestine to form the principal active benzodiazepine 8 chloro 6 2 chlorophenyl N N dimethyl 4H 1 2 4 triazolo 1 5 a 1 4 benzodiazepine 2 carboxamide 6 7 As can be seen in the molecular diagram below the principal metabolite contains a benzodiazepine ring structure i e a benzene ring fused with a diazepine ring unlike the parent compound rilmazafone which has no diazepine ring Rilmazafone active metaboliteSee also EditRilmazolam Avizafone Alprazolam triazolobenzophenone GL II 73References Edit DE Patent 2725164 Yamamoto K Hirose K Matsushita A Yoshimura K Sawada T Eigyo M Jyoyama H Fujita A Matsubara K Tsukinoki Y July 1984 Pharmacological studies of a new sleep inducer 1H 1 2 4 triazolyl benzophenone derivatives 450191 S I Behavioral analysis Nihon Yakurigaku Zasshi Folia Pharmacologica Japonica in Japanese 84 1 109 54 doi 10 1254 fpj 84 109 PMID 6149174 Yamamoto K Matsushita A Sawada T Naito Y Yoshimura K Takesue H Utsumi S Kawasaki K Hirono S Koshida H July 1984 Pharmacology of a new sleep inducer 1H 1 2 4 triazolyl benzophenone derivative 450191 S II Sleep inducing activity and effect on the motor system Nihon Yakurigaku Zasshi Folia Pharmacologica Japonica in Japanese 84 1 25 89 doi 10 1254 fpj 84 25 PMID 6149175 Ibii N Horiuchi M Yamamoto K August 1984 Pharmacology of a 1H 1 2 4 triazolyl benzophenone derivative 450191 S a new sleep inducer III Behavioral study on interactions of 450191 S and other drugs in mice Nihon Yakurigaku Zasshi Folia Pharmacologica Japonica in Japanese 84 2 155 73 doi 10 1254 fpj 84 155 PMID 6149177 Yasui M Kato A Kanemasa T Murata S Nishitomi K Koike K et al June 2005 Pharmacological profiles of benzodiazepinergic hypnotics and correlations with receptor subtypes Nihon Shinkei Seishin Yakurigaku Zasshi Japanese Journal of Psychopharmacology 25 3 143 51 PMID 16045197 Koike M Norikura R Sugeno K March 1986 Intestinal activation of a new sleep inducer 450191 S a 1H 1 2 4 triazolyl benzophenone derivative in rats Journal of Pharmacobio Dynamics 9 3 315 20 doi 10 1248 bpb1978 9 315 PMID 3454653 Muranushi N Miyauchi S Suzuki H Sugiyama Y Hanano M Kinoshita H Oguma T Yamada H May 1993 Comparative hepatic transport of desglycylated and cyclic metabolites of rilmazafone in rats analysis by multiple indicator dilution method Biopharmaceutics amp Drug Disposition 14 4 279 90 doi 10 1002 bdd 2510140402 PMID 8499579 S2CID 24923818 External links Edit リスミー リルマザホン塩酸塩水和物錠 Rhythmy rilmazafone hydrochloride hydrate tablets Prescribing Information PDF in Japanese Shionogi amp Co Ltd Drug Information Sheet Retrieved from https en wikipedia org w index php title Rilmazafone amp oldid 1137119299, wikipedia, wiki, book, books, library,
