돼지 우관상동백을 적출하여 항경련제인 oxybutynin의 약리작용을 조사하였다. 1. Acetylcholine (ACh)과 KCl은 관상동맥을 수축시켰고 이 수축효과는 용량의존적이었다. ACh의 수축효과는 내피손상표본 (EC<sub>50</sub>=0.52μM)에서 내피표본 (EC<sub>50</sub>=0.52μM)보다 약 2배 강화되있으나 KCl의 수축효과는 양군간에 차이가 없었다. 2. ACh(1.0μM)의 수축효과는 oxybutynin과 atropine에 의 하여 용량의존적으로 억제되었고 두 약물의 (IC<sub>50</sub>는 각각 11.0 nM과 0.47 nM로 atropine이 약 23배나 더 예민하였다. 그러나 KCl (35 mM)의 수축효과는 atropine으로는 전혀 영향받지 않았고 oxybutynin으로는 용량의존적으로 억제 되었으며 (IC<sub>50</sub>=49.7μM)이였다. 3. ACh의 용량반응곡선은 oxybutynin (IC<sub>50</sub>=11 nM) 및 atropine (IC<sub>50</sub>=0.47 nM) 전처 리 하에서 우측으로 평 행 이 동되 있고, KCI의 용량반응곡선은 oxybutynin (IC<sub>50</sub>=49.7 nM) 전처리하에서 우측으로 비상경적 이동을 일으켰다. 4. Oxybutynin은 Bay K 8644 (0.1μM)의 수축효과를 용량의존적 으로 억제하였고 (IC<sub>50</sub>=63.0μM)이었으며 , histamine (35μM)의 수축효과는 oxybutynin의 최대량 (500μM)으로 부분억제 (최대 50%)만을 일으켰다. 이상의 성적으로 적출돼지 관상동백에서 내피세포는 ACh에 의한 수축반응에 억제적 영향을 미치며, oxybutynin은 강력한 muscarine receptor 차단작용과 calcium influx 억제작용에 의하여 혈관근 이완을 일으킨다고 추론하였다.
Pharmacological actions of an antispasmodic agent, oxybutynin were investigated in the isolated procine coronary arteries. The coronary rings were contracted by acetylcholine (ACh) and KCl in a dose-dependent fashion. The ACh-induced contractions were signifcantly potentiated by removal of endothelium and EC<sub>50</sub>=0.52μM of intact endothelial rings was about 2 times greater than EC<sub>50</sub>=0.28μM of rings without the endothelium. These results suggest that the endothelium plays an inhibitory role in ACh-induced contraction. Oxybutynin and atropine inhibited dose-dependently 1.0μM ACh-induced contraction and atropine inhibited dose-dependently 1.0μM ACh-induced contraction and the IC<sub>50s</sub> were 11.0 nM and 0.47 nM, respectively. Atropine did not affect 35 mM KCl-induced contraction but oxybutynin inhibited the contraction to the basal tension in a dose-dependent manner. The IC<sub>50</sub> of oxybutynin on the KCl-induced contraction was 49.7μM. The dose-response curve to ACh was parallelly shifted to the right by pretreating coronary rings with IC<sub>50</sub> of atropine (0.47 nM) or oxybutynin (11.0 nM) but the curve to KC1 was rightward shifted in a noncompetitive manner under pretreatment with IC<sub>50</sub> of oxybutynin (49.7μM). Oxybutynin inhibited 0.1μM Bay K 8644-induced contraction to the basal tension in a dose dependent manner, but 35μM histamine-induced contraction was inhibited to only 50e/e of the original level even in maximal concentration (5 × 10<sup>-4</sup>M) of oxybutynin. These results suggest that oxybutynin causes antispasmodic action through sensitive blocking action on muscarinic receptors and inhibitory action on calcium influx in the procine coronary artery.