Epibatidine

unspecified strain^[1]

20 μg/kg; 13.6 μg/kg (ED₅₀, 5 minutes post-administration)

single dose

Produced decreased responsiveness to radiant heat in the mouse tail-flick test, with maximum antinociception occurring 5 minutes after administration and a duration of 20 minutes.
Achieved an ED₅₀ of 13.6 μg/kg for induced antinociception in mice 5 minutes after administration.
Showed similar antinociceptive activity across d-, i-, and r-isomers in the mouse tail-flick test.
Demonstrated no statistically significant change in ED₅₀ values compared to vehicle control when mice were pretreated with naloxone, yohimbine, or atropine, indicating the effect was not antagonized by these agents.

unspecified strain^[1]

4.3 μg/kg (ED₅₀)

single dose

Produced decreased responsiveness to radiant heat in the rat tail-flick test, with an ED₅₀ of 4.3 μg/kg.
Showed no blocked antinociceptive effect when rats were treated with naloxone or yohimbine.

C57BL/10J mice (male and female)^[4]

0.1 mg/kg

i.p.; single dose

Resulted in male mice having an epibatidine plasma concentration of 7.3 ng/mL 10 minutes post-injection.
Resulted in female mice having an epibatidine plasma concentration of 37.1 ng/mL 10 minutes post-injection, showing a significant sex-based difference in plasma levels.

Sprague-Dawley (male, 300-350 g)^[6]

0.005 μg; 0.05 μg; 0.5 μg

i.t.; single dose; repeated doses at 35-40 minute intervals

Elicited rapid onset pressor, tachycardia, and irritation responses, with irritation resolving and tachycardia shifting to bradycardia within 3-5 minutes; bradycardia peaked at ~7 minutes, pressor response remained above baseline for 15-20 minutes, intermittent irritation reappeared at 14-15 minutes, and all responses returned to baseline by 25-35 minutes.
Significantly reduced pressor, tachycardia, and irritation responses to subsequent doses, but did not affect bradycardia; cross-desensitized cardiovascular and behavioral responses to intrathecal cytisine and (-)-nicotine, with desensitization persisting to a plateau level that recovered within 2 hours.
Selectively inhibited analgesic response, showed no effect on pressor responses, had minor inhibitory effects on irritation responses to 0.5 μg, abolished bradycardia elicited by 0.05 μg, and increased irritation and tachycardia responses to 0.005 μg when pretreated with α-lobeline (50 μg, i.t.).
Significantly inhibited pressor responses to all three doses, inhibited irritation responses to 0.05 μg and 0.5 μg, blocked bradycardia elicited by 0.05 μg, and completely inhibited irritation responses 4 minutes after 0.5 μg administration when pretreated with methyllycaconitine (50 μg, i.t.).
Significantly inhibited initial pressor, tachycardia, and irritation responses to 0.5 μg, and potentiated the bradycardia response to this dose when pretreated with AP-5 (10 μg, i.t.).