Preclinical studies pertaining to the pharmacology and toxicology of
BMY 30123 (4-acetamidophenyl retinoate) are reported.
BMY 30123 is a novel compound which has topical
retinoid activity. This compound exhibits lower toxicity, both local and systemic, than other clinically used topical
retinoids such as
tretinoin (
all-trans retinoic acid) in animal models.
BMY 30123 is effective in a number of
retinoid sensitive skin models including the rhino mouse utriculi reduction assay, the mouse epidermal
hyperplasia model and in the suppression of
DNA synthesis in mouse skin stimulated with
phorbol ester.
BMY 30123 was equipotent with
tretinoin in these topical models. In the rhino mouse model the ED30 values for
BMY 30123 and
tretinoin were 0.037 and 0.015 mM, respectively. In addition,
BMY 30123 was active in the UVB-induced photodamaged mouse model, another
retinoid sensitive model. One of the problems associated with topically applied
tretinoin is local irritation. Therefore, for topical
therapy to be optimal, it is important to reduce or minimize local irritation. Repeated applications of
BMY 30123 to rabbit skin resulted in low skin irritation. The first perceptible signs of skin irritation produced by
BMY 30123 occurred at a dose 10 times higher than that observed for
tretinoin.
BMY 30123 also exhibits low
retinoid activity after oral or i.p. administration in mice and produced no signs of
hypervitaminosis A-related toxicity at twenty times the no effect dose of
tretinoin. Because
retinoids are effective modulators of epidermal growth and differentiation, this compound should be useful for the treatment of cutaneous disorders that exhibit altered epidermal differentiation such as
acne,
psoriasis,
ichthyosis and epithelial tumours.(ABSTRACT TRUNCATED AT 250 WORDS)