• The Korean Journal of Pharmacology
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• v.24 no.1
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• pp.93-101
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• 1988

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 $EC_{50}=0.52\;{\mu}M$ of intact endothelial rings was about 2 times greater than $EC_{50}=0.28\;{\mu}M$ 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 $1.0\;{\mu}M$ ACh-induced contraction and atropine inhibited dose-dependently $1.0\;{\mu}M$ ACh-induced contraction and the $IC_{50s}$ 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 $IC_{50}$ of oxybutynin on the KCl-induced contraction was $49.7\;{\mu}M$. The dose-response curve to ACh was parallelly shifted to the right by pretreating coronary rings with $IC_{50}$ 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 $IC_{50}$ of oxybutynin $(49.7\;{\mu}M$). Oxybutynin inhibited $0.1\;{\mu}M$ Bay K 8644-induced contraction to the basal tension in a dose dependent manner, but $35\;{\mu}M$ histamine-induced contraction was inhibited to only 50e/e of the original level even in maximal concentration $(5{\times}10^{-4}M)$ 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.

• Childhood Kidney Diseases
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• v.7 no.2
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• pp.174-180
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• 2003

Purpose : Unstable bladder has been known to be one of the reasons for the genesis and persistance of primary vesicoureteral reflux(VUR) in children. And treatment of unstable bladder by anticholinergic agent may contribute to the resolution of primary VUR. We evaluated the effect of an anticholinergic agent(oxybutynin) on the resolution of primary VUR in children with different toilet training and voiding functions. Methods : 152 children with persistant primary VUR after one year of follow up were randomly assigned to the oxybutynin group(n=59, oxybutynin 0.2 mg/kg twice daily) and the control group(n=93, no oxybutynin) at Ewha Womans University Mok-Dong Hospital from October 1996 to April 2002. The resolution rate of the VUR and the difference according to the status of toilet training and voiding dysfunction were analyzed. Statistical analysis was done by the Chi-square test and a P-value of less than 0.05 was considered as significant. Results : VUR was resolved in 49.2%, improved in 20.3% and not changed in 30.5% in the oxybutynin group(n=59) which was not significantly different to 45.2%, 16.1%, 38.7% in the control group(n=93), respectively. In the non-toilet trained young children, VUR was resolved in 50.0%, improved in 23.5% and not changed in 26.5% in the oxybutynin group(n=34) which was not significantly different to 44.2%, 19.2%, 36.6% in the control group(n=52), respectively. In the toilet trained older children, VUR was resolved in 48.0%, improved in 16.0% and not changed in 36.0% in the oxybutynin group(n=25) which was not significantly different to 46.3%, 12.2%, 41.5% in the control group(n=41), respectively. In the toilet trained older children with no voiding dysfunction, VUR was resolved in 33.3%, improved in 11.1% and not changed in 55.5% in the of oxybutynin group(n=9) which was not significantly different to 53.6 %, 10.7%, 35.7% in the control group(n=28), respectively. In the toilet trained older children with voiding dysfunction, VUR was resolved in 56.3%, improved in 18.7% and not changed in 25.0% in the oxybutynin group(n=16), which looked higher than 30.7%, 15.4%, 53.9% in the control group(n=13), respectively, but these were not significantly different either. Conclusion : Oxybutynin was not effective in the resolution of primary VUR in non-toilet trained young children and toilet trained older children. Oxybutynin showed slightly higher tendency of reflux resolution in toilet-trained older children with voiding dysfunction but the difference was not statistically significant. Judicious use of oxybutynin is required in selected older children with VUR and voiding dysfunction.

• The Korean Journal of Pharmacology
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• v.24 no.2
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• pp.203-216
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• 1988

To delineate the mechanisms of vasoconstriction and vasodilation in cerebral arteries the effects of some vasoconstrictors and calcium antagonists on the basilar artery (BA) and arterial circle of Willis (WC) were examined and also the role of endothelium in the action of these drugs was investigated in pigs, cats and rabbits. In pig cerebral arteries, dose-dependent contractile responses were elicited by KCI, histamine, 5-hydroxytryptamine (5-HT) and angiotensin, but norepinephrine (NE), phenylephrine (PE) and epinephrine (EP) elicited dose-dependent contractions only under pretreatment with propranolol 10-6 M. The magnitudes of maximal contractile effects of these drugs were different from each other, and 5-H~ was the largest and angiotensin the smallest. Some calcium antagonists dose-dependently inhibited KCI (35 mM)-induced contraction and the order of potency in inhibiting the contraction was nifedipine > > diltiazem > flunarizine > oxybutynin > isosorbide dinitrate (ISDN) > glyceryl trinitrate. 5-HT (10-6 M)-induced contraction was dosedependently inhibited by nifedipine but slightly inhibited by diltiazem and ISDN. In rings with intact endothelium, KCI (35 mM)-induced contraction was not affected by acetylcholine (ACh) but $PGF_{2{\alpha}}$ (lO-SM)-induced contraction was dose-dependently relaxed by ACh and adenosine. This endothelium-dependent relaxation was not affected by nifedipine (l0-6M)-pretreatment but markedly inhibited by methylene blue (50,uM)-pretreatment. In the porcine arterial rings without endothelium, ACh had no effect or even contracted the $PGF_{2{\alpha}}-induced$ contraction. However, the dosedependent relaxing effect of ACh appeared when the deendothelized porcine ring and rabbit thoracic aorta with intact endotheli urn were simultaneously suspended into a bath and this relaxing effect was also inhibited by methylene blue-pretreatment. In cat cerebral arteries, 5-HT and NE elicited dose-dependent contractile responses and ACh also produced dose-dependent contraction regardless of the existence of endothelium. ACh-induced contraction was most prominent. 5-HT (IO-SM)induced contraction was not relaxed but contracted additionally by ACh even in the intact endothelial ring. In rabbit cerebral arteries, 5-HT and NE elicited dose-dependent contractile responses and 5-HT-induced contraction was more prominent. In the intact endothelial preparations, 5-HT (lO-s M)-induced contraction was markedly relaxed by the addition of ACh( IO-SM) and this endothelium-dependent relaxing effect was inhibited by atropine (l0-7M)-pretreatment but notaffected by diltiazem (l0-6M)-pretreatment. These results suggest that ACh elicits endotheliumdependent relaxing effect mediated by muscarinic receptors in cerebral arteries of pig and rabbit, and that ACh acts as vasoconstrictor in cat cerebral artery.

• Korean Journal of Psychosomatic Medicine
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• v.31 no.2
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• pp.63-71
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• 2023

Urinary incontinence (UI), affecting 3%-11% of males and 25%-45% of females globally, is expected to rise with an aging population. It significantly impacts mental health, causing depression, stress, and reduced quality of life. UI can exacerbate psychiatric conditions, affecting treatment compliance and effectiveness. It is categorized into transient and chronic types. Transient UI, often reversible, is caused by factors summarized in the acronym DIAPPERS: Delirium, Infection, Atrophic urethritis/vaginitis, Psychological disorders, Pharmaceuticals, Excess urine output, Restricted mobility, Stool impaction. Chronic UI includes stress, urge, mixed, overflow, functional, and persistent incontinence. Drug-induced UI, a transient form, is frequently seen in psychiatric treatment. Antipsychotics, antidepressants, and other psychiatric medications can cause UI through various mechanisms like affecting bladder muscle tone, altering nerve reflexes, and inducing other conditions like diabetes or epilepsy. Specific drugs like lithium and valproic acid have also been linked to UI, though mechanisms are not always clear. Managing UI in psychiatric patients requires careful monitoring of urinary symptoms and judicious medication management. If a drug is identified as the cause, options include discontinuing, reducing, or adjusting the dosage. In cases where medication continuation is necessary, additional treatments like desmopressin, oxybutynin, trihexyphenidyl, or amitriptyline may be considered.