4-(2-(5-6-7-8-tetrahydro-5-5-8-8-tetramethyl-2-naphthalenyl)-1-propenyl)benzoic-acid and Body-Weight

4-(2-(5-6-7-8-tetrahydro-5-5-8-8-tetramethyl-2-naphthalenyl)-1-propenyl)benzoic-acid has been researched along with Body-Weight* in 2 studies

Other Studies

2 other study(ies) available for 4-(2-(5-6-7-8-tetrahydro-5-5-8-8-tetramethyl-2-naphthalenyl)-1-propenyl)benzoic-acid and Body-Weight

ArticleYear
Specific antagonist of retinoid toxicity in mice.
    Toxicology and applied pharmacology, 1996, Volume: 138, Issue:1

    AGN 193109 was recently identified as a potent retinoic acid receptor (RAR) antagonist in vitro. The purpose of the present study was to determine if AGN 193109 functions as an RAR antagonist in vivo and thus could prevent and/or treat retinoid toxicity. Female hairless mice were treated topically for 5 consecutive days with the synthetic retinoic acid receptor agonist (E)-4-[2-(5,6,7,8- tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)propen-1-yl]benzoic acid (TTNPB) alone or in the presence of a 1-, 4-, or 16-fold molar excess of AGN 193109. TTNPB caused skin flaking, skin abrasions, and splenomegaly, and these effects were blocked in a dose-dependent fashion by AGN 193109 cotreatment. In the same model, AGN 193109 also decreased topical irritation induced by the natural RAR agonist, all-trans-retinoic acid. To determine if topical AGN 193109 could block toxicity induced by an oral retinoid, mice were treated by gavage with TTNPB (0.75 mumol/kg/day) and topically with 0, 0.3, or 1.2 mumol/kg/day of AGN 193109 for 4 days. TTNPB treatment alone caused cutaneous irritation and weight loss, and these effects were inhibited by AGN 193109 cotreatment. To determine if AGN 193109 could be used to treat preexisting retinoid toxicity, mice were pretreated topically on Days 1-2 with TTNPB (0.72 mumol/kg/day) and then treated topically on Days 3-5 with 0, 1.44, 7.2, or 36.0 mumol/kg of AGN 193109. TTNPB pretreatment caused precipitous weight loss and, in the absence of AGN 193109 intervention, 60% mortality. AGN 193109 treatment at all dose levels significantly accelerated recovery of body weight and prevented death in TTNPB-intoxicated mice. These data demonstrate that AGN 193109 is a potent RAR antagonist and a potential antidote of retinoid intoxication in vivo. In addition to potential clinical applications in the prevention and treatment of retinoid toxicity, AGN 193109 should provide a powerful experimental tool for the elucidation of retinoid biology.

    Topics: Administration, Cutaneous; Animals; Benzoates; Body Weight; Female; Mice; Mice, Hairless; Naphthalenes; Organ Size; Receptors, Retinoic Acid; Retinoids; Spleen; Time Factors

1996
The growth-supporting activity of a retinoidal benzoic acid derivative and 4,4-difluororetinoic acid.
    Archives of biochemistry and biophysics, 1985, Feb-15, Volume: 237, Issue:1

    Two synthetic retinoids were examined for their ability to support growth in male vitamin A-deficient rats. One of the compounds, (E)-4-[2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1 -propenyl]-benzoic acid (TTNPB), was found to be highly effective; it was 35-fold more active than all-trans-retinoic acid. Thus, the in vivo results were in agreement with the in vitro activity of this compound published by previous investigators, and support the view that this compound may be useful in determining the molecular mechanism of action of the retinoids. Another analog, 4,4-difluororetinoic acid, was only 12% as effective as retinoic acid. However, the possible instability of this compound and the electronegativity of the fluoro groups prohibited conclusions concerning the biological function of metabolic modification on the 4 position of retinoic acid.

    Topics: Animals; Benzoates; Body Weight; Growth; Male; Rats; Retinoids; Tretinoin; Vitamin A Deficiency

1985