Reduction in ultraviolet B light-induced erythema by oxymetazoline and brimonidine is mediated by different α-adrenoceptors.

When applied topically, oxymetazoline and brimonidine reduce the persistent facial erythema of rosacea; this effect is mediated by cutaneous vasoconstriction induced by postsynaptic activation of α-adrenoceptors. We investigated the α-adrenergic pharmacology of oxymetazoline and brimonidine. Functional activity on α-adrenoceptors was evaluated in vitro in HEK293 cells stably expressing single receptor subtypes using a fluorometric imaging plate reader Ca2+ influx assay. Oxymetazoline was an α1 -adrenoceptor agonist with partial α2 -adrenoceptor activity, whereas brimonidine was a highly selective full α2 -adrenoceptor agonist. In vivo pharmacology was investigated in a mouse model of ultraviolet B light (UVB)-induced skin erythema. To selectively inhibit α-adrenoceptor subtypes, mice were injected with prazosin (an α1 -selective antagonist) or rauwolscine (an α2 -selective antagonist) following UVB exposure. Oxymetazoline cream 1.0%, brimonidine gel 0.33% or vehicle control was applied topically, and erythema was measured using a chromameter. Oxymetazoline and brimonidine reduced UVB-induced erythema compared with vehicle control (P < .01). The effect of oxymetazoline was impaired in prazosin-pretreated but not rauwolscine-pretreated mice. Conversely, the effect of brimonidine was impaired in rauwolscine-pretreated but not prazosin-pretreated mice. These data suggest that while oxymetazoline and brimonidine produce cutaneous vasoconstriction, they do so through different α-adrenergic mechanisms, with oxymetazoline primarily acting via α1 -adrenoceptors and brimonidine acting via α2 -adrenoceptors.