Rilmazafone

Rilmazafone
Clinical data
Trade namesRhythmy
Other names5-([(2-aminoacetyl)amino]methyl)-1-[4-chloro-2-(2-chlorobenzoyl)phenyl]-N,N-dimethyl-1,2,4-triazole-3-carboxamide
AHFS/Drugs.comInternational Drug Names
Routes of
administration		Oral (tablets)
ATC code
  • none
Legal status
Legal status
  • Rx-only (JP)
Pharmacokinetic data
Elimination half-life10.5 h
ExcretionUrine
Identifiers
  • 1-[4-chloro-2-(2-chlorobenzoyl)phenyl]-5-[(glycylamino)methyl]-N,N-dimethyl-1H-1,2,4-triazole-3-carboxamide
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC21H20Cl2N6O3
Molar mass475.33 g·mol−1
3D model (JSmol)
  • ClC1=C(C(C2=CC(Cl)=CC=C2N3C(CNC(CN)=O)=NC(C(N(C)C)=O)=N3)=O)C=CC=C1
  • 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) checkY
  • Key:KYHFRCPLIGODFH-UHFFFAOYSA-N checkY
  (verify)

Rilmazafone[1] (リスミー, Rhythmy, previously known as 450191-S) is a water-soluble prodrug developed in Japan.[2] Inside the human body, rilmazafone is converted into several benzodiazepine metabolites that have sedative and hypnotic effects.[3][4][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 rilmazolam (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.

Rilmazolam — an active metabolite
  1. ^ DE Patent 2725164
  2. ^ 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.
  3. ^ 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.
  4. ^ 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.
  5. ^ 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.
  6. ^ 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.
  7. ^ 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.