title: (R)- and (S)-4-Amino-3-(trimethylsilyl)methylbutanoic acids ameliorate neuropathic pain without central nervous system-related side effects.
abstract: Neuropathic pain is a chronic pain condition resulting from neuronal damage, and is usually treated with pregabalin or gabapentin, which are structurally related to γ-aminobutyric acid (GABA) and are originally developed as anticonvulsant drugs. Here, we report the synthesis and pharmacology of (R)- and (S)-4-amino-3-(trimethylsilyl)methylbutanoic acids (1a and 1b), which showed analgesic activity as potent as that of pregabalin in the Chung spinal nerve ligation model. However, unlike pregabalin, 1a and 1b do not have antiepileptic effects, and they are therefore promising candidates for selective therapeutic agents to treat neuropathic pain without central nervous system-related side effects.
authors.affiliation: Research Foundation ITSUU Laboratory, 2-28-10 Tamagawa, Setagaya-ku, Tokyo 158-0094, Japan. hmuratake@itsuu.or.jp
authors.forename: Hideaki
authors.initials: H
authors.lastname: Muratake
authors.forename: Ai
authors.initials: A
authors.lastname: Ito
authors.forename: Takahiro
authors.initials: T
authors.lastname: Toda
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Suzuki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Fukasawa
authors.forename: Makoto
authors.initials: M
authors.lastname: Tsuda
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Inoue
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Sugiyama
authors.forename: Koichi
authors.initials: K
authors.lastname: Shudo
mesh_terms: D000700:Analgesics / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use*; D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use*; D002087:Butyrates / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use*; D002493:Central Nervous System Diseases / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D015394:Molecular Structure; D009437:Neuralgia / Q000188:drug therapy*; D051381:Rats; D013237:Stereoisomerism; D014297:Trimethylsilyl Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use*
chemical_list: C581082:(S)-4-amino-3-(trimethylsilyl)methylbutanoic acid; D000700:Analgesics; D000927:Anticonvulsants; D002087:Butyrates; D014297:Trimethylsilyl Compounds