痙攣性 腦-電氣衝擊에 의한 생쥐 視床下部 및 腦幹의 Monoamine 代謝의 變動에 관한 硏究

全普權,申炅浩,朴靑山,李明雅 大韓神經精神醫學會 1991 신경정신의학 Vol.30 No.4

Male ICR mice ranging from 15g to 20g were given a single ECS(1-ECS : 13mA, 1sec,100cps) daily or on alternate days for 10 days(5-ECS). The contents of monoamine metabolites in the hypothalamus and the brain stem(BS) were measured 10, 30. and 60 min after ECS-administration as well as before ECS. Contents of monoamine metabolites in the HT and the BS, such as 5-HIAA, MHPG, DOPAC and HVA increased rapidly after 1-ECS or 5ECS and then came down to the pre-ECS values. However, their increases induced by 5-ECS were significantly smaller than those by 1-ECS except the tedious increase of the hypothalamic HAV content. 5-HIAA and MHPG in the HT decrease significantly by the 4the administration of ECS in the course of the 5-ECS treatment. These results suggest that the repeated treatment of ECS may decrease the turnover rates of serotonin and noradrenaline in the hypothalamus.

알코올의 약리작용

全普權 대한의사협회 1998 대한의사협회지 Vol.41 No.1

Morphine에 依한 組織 Catecholamine含量의 變動에 미치는 Clonidine의 影響

李哲毅,全普權,申萬鍊 고려대학교 의과대학 1984 고려대 의대 잡지 Vol.21 No.1

It has been well known that noradrenaline neurons appear to be involved in both morphine and clonidine analgesia, and there are many evidences that the effects of the two drugs on brain noradrenaline-turnover are inhibitory. But the functional role of brain noradrenaline in the suppressive effect of clonidine on the development of opioid withdrawal signs has not yet been clarified. The present study was therefore undertaken in order to ascertain whether brain noradrenaline is responsible for clonidine-induced suppression of development of development of opioid withdrawal signs or cross-tolerance to morphine and clonidine, and so, seventeen hours after the last of 12 injections of increasing doses of both morphine and clonidine over 6 days according to the modified Paalzow’s and Weinstock’s and Weinstock’s methods of the development of tolerance to the two drugs of morphine and clonidine on brain and heart catecholamine contents were estimated in male mice. The results obtained were summarized as follows: 1. Morphine (20㎎/㎏ i.p.) slightly increased brain catecholamine content and significantly increased heart catecholamine content. The morphine-induced increase of brain catecholamine content was not altered all along the 7 day treatment of it, but the morphine-induced increase of heart catecholamine content was augmented after the 4 day treatment of it and the augmentation showed a moderate decline after the 7 day treatment. 2. Clonidine (500㎍/㎏ i.p.) significantly increased both brain and heart catecholamine contents. The clonidine-induced increase of brain catecholamine content was not altered all along the 7 day treatment of it, but the clonidine-induced increase of heart catecholamine content was slightly augmented after the 4 day treatment of it and then recovered to the initial level. 3. The combined effect of morphine and clonidine on the both brain and heart catecholamine contents was additive, and the additive combined-effect was not altered all along the 7 day treatment of the two drugs. The above results suggest that the tolerance development of morphine and the clonidineinduced suppression of opioid withdrawal signs may be mediated through other neuronal systems as well as noradrenergic system.

Morphine의 血漿 Corticosterone增加作用에 미치는 Clonidine과 Alpha-Methyldopa의 抑制性 效果의 比較

洪基成,全普權,申萬鍊 고려대학교 의과대학 1986 고려대 의대 잡지 Vol.23 No.1

There is much disagreement on the role of adrenoceptor in the ACTH liberation from the adenohypophysis. In this paper, the influences of several adrenoceptor blockades on the inhibitory effect of clonidine and alpha-methyldopa on the morphine-induced increase of plasma corticosterone level in male mice were studied. The results obtained were summarized as follows; 1. Clonidine(100 and 500㎍/kg), alpha-methyldopa(30 and 230mg/kg) and naloxone(1 and 4mg/kg), respectively, showed the dose-dependent inhibitory effect on the morphine-induced increase of plasma corticosterone level. 2. Clonidine(500㎍/kg) did not affect the increase induced by- ACTH(5U/kg), picrotoxin (4mg/kg) or cold-swim stress of plasma corticosterone level. 3. Alpha-methyldopa( 250mg/kg) did not affect the ACTH-induced increase of plasma corticosterone level but significantly suppress the picrotoxin-induced increase, and it rather enhanced the increase induced by cold-swim of plasma corticosterone level. 4. The inhibitory effect of clonidine on the morphine-induced increase of plasma corticosterone level was not affected by prazosin(1mg/kg), propranolol(1mg/kg) and haloperidol (1mg/kg) but significantly suppressed by phenoxybenzamine(1mg/kg) and yohimbine(1mg/kg). 5. The inhibitory effect of alpha-methyldopa on the morphine-induced increase was not affected by prazosin and haloperidol but significantly suppressed by phenoxybenzamine, yohimbine and propranolol. These results suggest that the inhibitory effect of clonidine on the morphine-induced increase of plasma corticosterone level may be mainly mediated by its property as an alpha₂-adrenoceptor agonist, but the inhibitory effect of alpha-methyldopa may be somewhat different from that of clonidine and may be mediated by its action as alpha₂-adrenoceptor agonist and other nonselective actions.

Pentazocine의 鎭痛效果에 미치는 Diazepam과 Naloxone의 影響

廉英鶴,全普權,申萬鍊 고려대학교 의과대학 1982 고려대 의대 잡지 Vol.19 No.3

In this paper, the analgesia and the change induced by pentazocine of plasma corticosterone level and blood sugar level in mice were assayed, and also the influences of diazepam and naloxone on those effects of pentazocine were studied. The results obtained were summarized as follows; 1. The threshold temperature of pain induction (TTPI) was determined as a index of the response to a painful stimulus using a hotplate. Diazepam 2.5㎎/㎏ and naloxone 1.0 ㎎/㎏ moderately increased TTPI, respectively, and the analgesic effect of pentazocine 3.16㎎/㎏, 10㎎/㎏, or 31.6 ㎎/㎏, showed a log dose-dependent response curve. The response curve to pentazocine was shifted to the right by the pretreatment of naloxone, but it was shifted to the left by the pretreatment of diazepm. 2. Diazepam 5.0㎎/㎏ and pentazocine 30㎎/㎏ significantly increased the plasma corticosterone level. And the increase induced by pentazocine of plasma corticosterone was not suppressed by the pretreatment of naloxone but by the pretreatment of diazepam. 3. Diazepam 5.0㎎/㎏ and pentazocine 30㎎/㎏ transiently increaesd the blood sugar level, and the increase induced by pentazocine was not affected by the pretreatment of either naloxone or diazepam. This study suggests that the pentazocine receptor to increase the plasma corticosterone level is different from that to induce the pentazocine analgesia.

Morphine의 血漿Corticosterone增加作用에 對한 Clonidine의 抑制效果에 미치는 Adrenoceptor 遮斷劑의 影響

田溶愛,全普權,申萬鍊 고려대학교 의과대학 1984 고려대 의대 잡지 Vol.21 No.1

Clonidine is a potent, centrally acting, antihypertensive that produces analgesia and suppresses the opioid withdrawal signs. Ganong et al. reported that catecholamine and clonidine inhibit the ACTH liberation from an anterior pituitary gland. In order to ascertain whether the suppression induced by clonidine of morphine-induced increase of plasma corticosterone level is related with the stimulation of alpha-s-adrenoceptor, the influences of phenoxybenzamine, yohimbine, and propranolol on the suppression induced by clonidine of morphine-induced increase of plasma corticosterone level in male mice. The results obtained were summarized as follows: 1. Clonidine 100㎍/㎏ or 500㎍/㎏ did not affect the basal plasma corticosterone level. 2. Plasma corticosterone level was slightly increased by phenoxybenzamine 10㎎/㎏ or yohimbine 5㎎/㎏. 3. Plasma corticosterone level was significantly increased by morphine 20㎎/㎏, ACTH 5㎍/㎏ and picrotoxin 4㎎/㎏. And the morphine-induced increase was not affected by the clonidine 100㎍/㎏ but significantly suppressed by the clonidine 500㎍/㎏. But the ACTH or picrotoxin-induced increase was not affected by even the clonidine 500㎍/㎏. 4. The suppressing effect of clonidine 500㎍/㎏ on the morphine-induced increase was not affected by the pretreatment of propranolol 5㎎/㎏ but significantly inhibited by the pretreatment of phenoxybenzamine 10㎎/㎏ or yohimbine 5㎎/㎏. The results suggest that clonidine dose not affect the basal level of plasma adrenal corticosteroid and suppression mechanism of clonidine on the morphine-induced increase of plasma corticosterone level is mediated through the stimulation of alpha-2-adrenoceptor.

Morphine의 血漿 Corticosterone 增加作用에 미치는 副交感神經系藥物의 影響

文永煥,全普權,申萬鍊 고려대학교 의과대학 1987 고려대 의대 잡지 Vol.24 No.1

Buckingham suggested that the effects of opioid substances on CRF secretion are probably due partially to direct actions on the hypothatamus and partially to alterations in the activity of cholinergic and noradrenergic neurons in the central nervous system. In this paper, the influences of cholinergic and anticholinergic drugs on the morphine-induced increase of plasma corticotserone level was studied in male mice. The results obtained were summarized as follows; 1. The dose-dependent increasing effect of morphine on plasma corticosterone was significantly inhibited by naloxone. 2. Pilocarpine (0.1-2.0㎎/㎏), physostigmine(10-200㎍/㎏), carbachol(10-200㎍/), and nicotine(0.1-2.0㎎/㎏) induced the dose-dependent increase of plasma corticosterone level. Particularly, the increasing effect of physostigmine and carbachol was marked. 3. The increasing effect of morphine on plasma corticosterone was markedly enhanced by pilocarpine, physostigmine or carbachol and was slightly enhanced by nicotine. The combined effect of morphine with pilocarpine or nicotine showed a tendency to be strengthened by atropine. But the combined effect of morphine and physostigmine was little changed by atropine and the combined effect of morphine and carbachol was inclined to be decreased by atropine. 4. Atropine(1.0㎎/㎏)and hexamethonium(10㎎/㎏)induced the marked increase of plasma corticosterone level. But by the combined treatment of them, the plasma corticosterone level showed the initial marked increase followed by the abrupt decrease downward to the control level. The increase induced by the combined treatment of atropine or hexamethonium with morphine was rather lower than that induced by a single treatment of atropine or hexamethonium. These results suggest that the increasing effect of morphine on plasma corticosterone level is mediated rather by its direct action on hypothalamus and its indirect action on central noncholiergic neurones than by its action on central cholinergic neuronal function.

Morphine의 血漿 Corticosterone 增加作用에 미치는 Clonidine의 影響

金泰洪,全普權,申萬鍊 고려대학교 의과대학 1983 고려대 의대 잡지 Vol.20 No.3

Clonidine, a potent antihypertensive drug, has other pharmacological effects, including analgesia, reduction of opiate withdrawal intensity, anxiolytic effect, and so on. In this paper, the influence of clonidine on the morphine-induced increase of plasma corticosterone level was investigated in male mice. The obtained results were summarized as follows; 1. The tolerance to the morphine-induced increase of plasma corticosterone level was rapidly developed within one week, and the development of tolerance was not affected by clonidine. 2. Acute administration of clonidine did not significantly change the normal plasma corticosterone level, but the morphine-induced increase of plasma corticosterone level was markedly suppressed by the pretreatment of clonidine. 3. The plasma corticosterone level at 10 hours after the cessation of the long-term (7 days) medication of morphine, clonidine or clonidine plus morphine was, respectively, much lower than that of the control group.

Morphine의 血糖 및 血奬 Corticosterone 增加作用에 미치는 Naloxone과 Dexamethasone의 影響

朴靑山,全普權,申萬鍊 고려대학교 의과대학 1985 고려대 의대 잡지 Vol.22 No.1

There are still considerable debates as to the similarity of opioid receptor and ACTH receptor and the interrelationships between opioid peptides and ACTH in the adrenal sterolidogenesis. To evaluate the interrelationships between opioid peptides and ACTH in the adrenal steroidogenesis and the role of the catecholamines liberated by opioid substances in the above interrelationships, the influences of naloxone and dexamethasone on the changes induced by morphine and ACTH of plasma corticosterone and blood sugar levels and the interactions between morphine and ACTH on those levels were studied in male mice. The results obtained were summarized as follows; 1. The normal plasma corricoscerone was not affected by dexamethasone 5mg/Kg, but markedly increased by morphine 20mg/Kg, naloxone 4mg/Kg, and ACTH 10U/Kg, respectively. 2. The morphine-induced increase of plasma corticosterone level was markedly inhibited by the pre- or post-treatment of naloxone and dexamethasone, respectively, and the inhibitory effect of each of naloxone and dexamethasone was appeared synergistically. 3. The ACTH-induced increase of plasma corticosterone level was moderately inhibited by naloxone pretreatment but not affected by naloxone posttreatment and pre- or post- treatment of dexamethasone, and the inhibitory effect of naloxone was significantly attenuated by dexamethasone. 4. The ACTH-induced increase of plasma corticosterone level was significantly augmented by morphine pretreatment, and the augmented increase of the level was not affected by naloxone, but the increase induced by ACTH followed by morphine of plasma corticosterone level was significantly inhibited by naloxone. 5. The normal blood sugar level was not affected by ACTH 10U/Kg, but markedly increased by morphine 20mg/Kg, naloxone 4mg/Kg and dexamethasone 5mg/Kg, respectively. 6. The morphine-induced increase of blood sugar level was significantly attenuated by each of naloxone and dexamethasone, but not affected by the combined treatment of naloxone and dexamethasone. The above results suggest that the morphine-induced increase of plasma corticosterone level is appeared mainly by its stimulation of hypothalamo-pituitary system and also partly by its interaction with ACTH on the adrenal cortex, that the morphine-induced increases of plasma corticosterone and blood sugar are significanly attenuated by dexamethasone as well as naloxone, and also that it is difficult that the catecholamine liberated by morphine appears a meaningful effect on the morphine-induced increase of plasma corticosterone level.

Morphine의 血漿 Corticosterone增加作用에 對한 Clonidine의 抑制性 效果에 있어서 Monoamine性 神經系의 關聯性에 關한 硏究

韓泰熙,全普權,申萬鍊 고려대학교 의과대학 1986 고려대 의대 잡지 Vol.23 No.1

Buckingham suggested that the effects of opioid substances on CRF secretion are probably-due partially to direct actions on the hypothalamus and partially to alterations in the ratio of stimulatory and inhibitory signals received from higher centers i3 the brain. And there are several reports supporting that the inhibitory effect of clonidine on the morphine-induced increase of plasma corticosterone level may be mediate3 by its property as an alpha₂-adrenoceptor agonist. In this paper, tire influences of alteration of moncaminergic neuoronal activities on the inhibitory effect of clonidine on the morphine-induced increase of plasma corticosterone level were studied in male mice. The results obtained were summarized as follows; 1. Clonidine(100 and 500 ㎍/kg) slightly increased plasma corticosterone level in normal mice, and the increasing effect of clonidine was not affected by iproniazid(100 mg/kg) and p-chlorophenylalanine (400 mg/kg) but significantly enhanced by reserpine(2 mg/kg) and alpha-methyl-p-tyrosine(250 mg/kg). 2. Clonidine(100 and 50 0㎍/kg) showed the dose-depeiident inhibitory effect on the morphine-induced increase of plasma corticosterone level. 3. The inhibitory effect of clonidine(100 ㎍/kg) on the morphine-induced increase of plasma corticosterone level was not affected by iproniazid but moderately suppressed by reserpine, alpha-methyl-p-tyrosine, and p-chlorophenylalanine. 4. The inhibitory effect of clonidine(500 ㎍/kg) on the morphine-induced increase of plasma corticosterone level was cot affected by reserpine, iproniazid, alpha-methyl-p-tyrosine, and p-chlorophenylalanine. These results suggest that the inhibitory effect of clonidine on the morphine-induced increase of plasma corticosterone level are probably due partially to its direct action on the hypothalamo-adenohypophyseal system rather than due to its indirect (presynaptic) action on the morphine-induced changes of central moncaminergic neuronal activities.