Elucidation of the profound antagonism of contractile action of phenylephrine in rat aorta effected by an atypical sympathomimetic decongestant

• 영문명: Elucidation of the profound antagonism of contractile action of phenylephrine in rat aorta effected by an atypical sympathomimetic decongestant
• 발행기관: 대한생리학회-대한약리학회
• 저자명: Eldina Rizvić Goran Janković Miroslav M. Savić
• 간행물 정보: 『The Korean Journal of Physiology & Pharmacology』제21권 제4호, 385~395쪽, 전체 11쪽
• 주제분류: 의약학 > 의학일반
• 파일형태: PDF
• 발행일자: 2017.01.01

영문 초록

Vasoconstrictive properties of sympathomimetic drugs are the basis of their widespread use as decongestants and possible source of adverse responses. Insufficiently substantiated practice of combining decongestants in some marketed preparations, such are those containing phenylephrine and lerimazoline, may affect the overall contractile activity, and thus their therapeutic utility. This study aimed to examine the interaction between lerimazoline and phenylephrine in isolated rat aortic rings, and also to assess the substrate of the obtained lerimazoline-induced attenuation of phenylephrine contraction. Namely, while lower concentrations of lerimazoline (10^–6 M and especially 10^–7 M) expectedly tended to potentiate the phenylephrine-induced contractions, lerimazoline in higher concentrations (10^–4 M and above) unexpectedly and profoundly depleted the phenylephrine concentration-response curve. Suppression of NO with NO synthase (NOS) inhibitor N^w-nitro-L-arginine methyl ester (L-NAME; 10^–4 M) or NO scavanger OHB₁₂ (10^–3 M), as well as non-specific inhibition of K⁺-channels with tetraethylammonium (TEA; 10^–3 M), have reversed lerimazoline-induced relaxation of phenylephrine contractions, while cyclooxygenase inhibitor indomethacin (10^–5 M) did not affect the interaction between two vasoconstrictors. At the receptor level, non-selective 5-HT receptor antagonist methiothepin reversed the attenuating effect of lerimazoline on phenylephrine contraction when applied at 3×10^–7 and 10^–6 M, but not at the highest concentration (10^–4 M). Neither the 5-HT_1D-receptor selective antagonist BRL 15572 (10^–6 M) nor 5-HT₇ receptor selective antagonist SB 269970 (10^–6 M) affected the lerimazoline-induced attenuation of phenylephrine activity. The mechanism of lerimazoline-induced suppression of phenylephrine contractions may involve potentiation of activity of NO and K⁺-channels and activation of some methiothepin sensitive receptors, possibly of the 5-HT_2B subtype.

키워드

Aorta Decongestant Lerimazoline Phenylephrine Potentiation