TAAR1-Associated Trace Amines for Cutaneous Nociceptive Blockade in Rats

This study aimed to evaluate whether TAAR1 (trace amine-associated receptor 1)-associated trace amines (β-phenylethylamine, tryptamine, octopamine, tyramine, and N-methyltyramine) produced cutaneous nociceptive blockade compared to lidocaine. Cutaneous nociceptive blockade was assessed by inhibition of the cutaneous trunci muscle reflex in response to local noxious stimuli. After subcutaneous injection in rats, the nociceptive blockade produced by β-phenylethylamine, tryptamine, octopamine, tyramine, and N-methyltyramine was compared. We demonstrated that, at a dose of 255.3 μmol/kg, β-phenylethylamine, tryptamine, octopamine, tyramine, and N-methyltyramine produced cutaneous nociceptive blockade. At the ED₅₀ (50% effective dose), the relative potency of β-phenylethylamine (85.5 [87.5-93.2] μmol/kg) was lower than that of lidocaine (17.7 [14.6-2.15] μmol/kg; p < 0.01). On an equianesthetic basis (ED₂₅, ED₅₀, and ED₇₅), β-phenylethylamine exhibited a duration of action similar to that of lidocaine. The addition of clonidine or epinephrine did not prolong the duration of action of β-phenylethylamine, whereas the addition of clonidine or epinephrine prolonged the duration of action of lidocaine. Among these five TAAR1-associated trace amines, β-phenylethylamine was the most potent for producing cutaneous nociceptive blockade, tryptamine and octopamine were moderately potent, and tyramine and N-methyltyramine were the least potent. Although β-phenylethylamine was less potent than lidocaine, it exhibited a similar duration of action. Clonidine and epinephrine did not prolong the duration of action of β-phenylethylamine.