(R)- and (S)-4-Amino-3-(trimethylsilyl)methylbutanoic acids ameliorate neuropathic pain without central nervous system-related side effects

Hideaki Muratake, Ai Ito, Takahiro Toda, Hideyuki Suzuki, Hiroshi Fukasawa, Tsuda Makoto, Kazuhide Inoue, Kiyoshi Sugiyama, Koichi Shudo

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)7602-7604
Number of pages3
JournalBioorganic and Medicinal Chemistry Letters
Volume22
Issue number24
DOIs
Publication statusPublished - Dec 15 2012

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Neurology
Neuralgia
Central Nervous System
Anticonvulsants
Aminobutyrates
Spinal Nerves
Chronic Pain
gamma-Aminobutyric Acid
Ligation
Analgesics
Pharmacology
(S)-4-amino-3-(trimethylsilyl)methylbutanoic acid
Pregabalin
Therapeutics

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Cite this

(R)- and (S)-4-Amino-3-(trimethylsilyl)methylbutanoic acids ameliorate neuropathic pain without central nervous system-related side effects. / Muratake, Hideaki; Ito, Ai; Toda, Takahiro; Suzuki, Hideyuki; Fukasawa, Hiroshi; Makoto, Tsuda; Inoue, Kazuhide; Sugiyama, Kiyoshi; Shudo, Koichi.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 22, No. 24, 15.12.2012, p. 7602-7604.

Research output: Contribution to journalArticle

Muratake, Hideaki ; Ito, Ai ; Toda, Takahiro ; Suzuki, Hideyuki ; Fukasawa, Hiroshi ; Makoto, Tsuda ; Inoue, Kazuhide ; Sugiyama, Kiyoshi ; Shudo, Koichi. / (R)- and (S)-4-Amino-3-(trimethylsilyl)methylbutanoic acids ameliorate neuropathic pain without central nervous system-related side effects. In: Bioorganic and Medicinal Chemistry Letters. 2012 ; Vol. 22, No. 24. pp. 7602-7604.
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