Gamma-aminobutyric acid amides of nortriptyline and fluoxetine display improved pain suppressing activity.
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.
Rephaeli
Ada
A
Laboratory of Pharmacology and Experimental Oncology, Felsenstein Medical Research Center, Sackler Faculty of Medicine, Tel-Aviv University, Ramat Aviv, Israel. adarep@post.tau.ac.il
Gil-Ad
Irit
I
Aharoni
Ana
A
Tarasenko
Igor
I
Tarasenko
Nataly
N
Geffen
Yona
Y
Halbfinger
Efrat
E
Nisemblat
Yotam
Y
Weizman
Abraham
A
Nudelman
Abraham
A
D000700:Analgesics / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000928:Antidepressive Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D001007:Anxiety / Q000139:chemically induced / Q000188:drug therapy; D001522:Behavior, Animal / Q000187:drug effects; D005473:Fluoxetine / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D005557:Formaldehyde / Q000633:toxicity; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy; D008297:Male; D051379:Mice; D009661:Nortriptyline / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy*; D051381:Rats; D005680:gamma-Aminobutyric Acid / Q000737:chemistry*
D000700:Analgesics; D000928:Antidepressive Agents; D005473:Fluoxetine; D005557:Formaldehyde; D005680:gamma-Aminobutyric Acid; D009661:Nortriptyline