Clonidine에 의하여 변화된 Catechlamine과 그 합성효소활성에 미치는 삼환계 항우울약의 영향

Abstract

중추성 혈압강하제 clonidine은 임상적으로 삼환계 항우울약과 병용투여시 혈압강하작용이 감소된다는 보고가 있어 그 기전을 규명하고자 흰쥐를 사용하여 clonidine을 투여하였을 때와, imipramine과 병용투여시 뇌 각부위, 부신의 Catecholamine함량과 Tyrosine Hydroxyl ase(T.H.)Activity, Phenylethanolamine N-methyl Transferase(P.N.M.T.)Activity를 측정하여 삼환계 항우울약이 clonidine투여시의 Norepinephrine(NE) 유리와 Catecholamine합성효소에 미치는 영향을 검토하여 다음과 같은 결론을 얻었다. 1. Clonidine투여시 뇌간, 시상하부에서 NE양이 대조군에 비하여 80%, 177%증가하였으며 유의적(P＜0.05)이었다. 2. Clonidine과 imipramine병용투여시 뇌간 NE 양이 clonidine군에 비하여 47%로 감소하였고 유의적 (P<0.05)이었다. 3. Clonidine투여시 뇌중 T.H. activity는 뇌간에서 대조군에 비하여 52%로 감소하였고 유의적(P<0.05)이었다. 4. Clonidine과 imipramine 병용투여시 뇌중 T.H. activity는 뇌간에서 clonidine군에 비하여 88% 증가하였고 유의적(P<0.001)이었으며, 시상하부에서는 277% 증가하였고 유의적(P<0.05)이었다. 5. 부신의 P.N.M.T. activity는 clonidine투여시 대조군에 비하여, clonidine, imlpramine병용투여시 clonidine투여군에 비하여 유의적인 차이가 없었다.;From clinical experiences it has been known that the hypotensive action of clonidine via the C.N.S. may be antagonized by Tricyclie Antidepressants. Thus the experiment was set up to investigate the interaction of Tricyclic Antidepressant imipramine with clonidine by measuring Catecholamine Concentration and Tyrosine Hydroxytase Activity and Phenylethanolamine N-methyl Transferase Activity in brain and adrenal of rats which administered with clonidine, imipramine and with only clonidine. The summarized results are as follows ; 1. In the cage of clonidine (100 g/kg, twice daily for 5 days) administration, the NE concentration in Brainstem and Hypothalamus was significantly increased (p<0.05) by 80%, 177% of the value of control. 2. In the case of clonidine (100μg/kg, twice daily for 5 days) and imipramine(10mg/kg, given 26hr and 5hr before decapitation) administration the NE concentration in Brainstem) was significantly reduced (p<0.001) to 47% of the value of clonidine alone. 3. In the case of clonidine (100μg/kg, twice daily for 5 days) administration, the T.H. activity in Brainstem was significantly reduced (p<0.05) to 52 % of the value of control. 4. In the case of clonidine (100μg/kg, twice daily for 5 days) and imipramine (10mg/kg, given 26hr and 5hr before decapitation) administration, the T.H. activity in Brainstem and Hypothalamus was significantly increased (p<0.001, p<0.05) by 88%, 277% compared with clonidine alone. 5. In the case of clonidine (100μg/fg, twice daily for 5 days) administration, the P.N. M.T. activity in Adrenal was not different from the value of control. And when clonidine (100μg/kg, twice daily for 5 days) and imipramine (10mg/kg, given 26hr and 5hr before decapitation) were administered, the P.N.M.T. Activity in Adrenal was not different from the value of clonidine. According to the results, the effect of increasing brain regional NE content and adrenal NE, Epi. content by clonidine, is due to the inhibitory action of NE release in synaptic cleft. So increasing NE content in presynaptic axon results in the decrease of T.H.activity. Tricyclic Antidepressants antagonize the effect of increasing brain regional N.E content by clonidine. This is due to the blockade of NE neuronal reuptake. Thus decreasing NE, content in presynaptic axon results in the increase of T.H.activity.