Gamma-aminobutyric acid amides of nortriptyline and fluoxetine display improved pain suppressing activity.

Abstract

The GABA amides of the antidepressants nortriptyline and fluoxetine, 1 and 2, were compared to their respective parent compounds in rodent models of pain. The amides significantly reduced early nociceptive and late inflammatory responses compared to nortriptyline or fluoxetine, where 1 exhibited overall better efficacy than 2. Amide 1 was most efficacious in lowering cytokine secretion, edema and hyperalgesia induced by formalin and lambda-carrageenan, respectively. Thus, 1 is a promising candidate for the treatment of pain.

• Authors: Ada Rephaeli, Irit Gil-Ad, Ana Aharoni, Igor Tarasenko, Nataly Tarasenko, Yona Geffen, Efrat Halbfinger, Yotam Nisemblat, Abraham Weizman, Abraham Nudelman
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 52 Issue 9 Pg. 3010-7 (May 14 2009) ISSN: 1520-4804 [Electronic] United States
• PMID: 19378992 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Analgesics
• Antidepressive Agents
• Fluoxetine
• Formaldehyde
• gamma-Aminobutyric Acid
• Nortriptyline

Topics

• Analgesics (chemical synthesis, chemistry, pharmacology, therapeutic use)
• Animals
• Antidepressive Agents (chemical synthesis, chemistry, pharmacology, therapeutic use)
• Anxiety (chemically induced, drug therapy)
• Behavior, Animal (drug effects)
• Fluoxetine (chemical synthesis, chemistry, pharmacology, therapeutic use)
• Formaldehyde (toxicity)
• Inflammation (chemically induced, drug therapy)
• Male
• Mice
• Nortriptyline (chemical synthesis, chemistry, pharmacology, therapeutic use)
• Pain (chemically induced, drug therapy)
• Rats
• gamma-Aminobutyric Acid (chemistry)