• Journal of Pharmaceutical Investigation
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• v.9 no.2
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• pp.22-30
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• 1979

Effects of Akebiae Lignum, whose scientific name is Akebia quinata Decaisne, on the blood pressure were investigated with EtOH extract in whole and spinal rabbits. Akebia Lignum EtOH extract (AEE), when given intravenously, produced a fall in blood pressure not only in whole rabbit but also in spinal rabbit and AEE administered into a lateral cerebral ventricle of whole rabbit did not elicit a fall in blood pressure. The depressor responses of the whole rabbit to intravenous AEE were weakened by treatment of the animals with atropine and chlorisondamine but not by vagotominijation, phentolamine avil, and then the depressor action causing by AEE in the whole rabbit was not affected by pretreatment of physostigmine which is cholinesterase inhibitor and of hemicholinium which blocks acetylcholine synthesis by interfering with choline uptake in nerves. These observations suggest that the hypotensive action of AEE of which component is not affected by cholinesterase is due to direct action at parasympathetic receptor.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1999.04a
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• pp.1-4
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• 1999

The potential therapeutic benefit of nicotinic ligands in a variety of neurodegenerative pathologies involving the CNS has energized research efforts to develop nicotinic acetylcholine receptor (nAChR) subtype-selective ligands. In particular, there has been a concerted effort to develop nicotinic compounds with selectivity for CNS nAChRs as potential pharmacological tools in the management of these disorders. The characterization of other novel nicotinic ligands such as epibatidine. showing a marked increase in potency at nAChRs, has provided additional support for the development of potent, selective ligands at individual nAChR subtypes. We have developed and studied a number of nicotinic compounds to identify potential candidates exhibiting such selectivity. In the present study, we report the synthesis and biological evaluations of some azabicyclic and azatricyclic nicotine analogs to decipher the relationship among steric requirements of the nicotine's pyrrolidine ring system, binding affinity and subtype-selectivity.

• Bulletin of the Korean Chemical Society
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• v.27 no.11
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• pp.1741-1746
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• 2006

3D-QSARs on the neuroblocking activities by 1-(6-chloro-3-pyridylmethyl)-2-nitroiminoimidazolidine analogues as agonist at the nicotinic acetylcholine receptor (nAChR) were studied quantitatively using CoMFA and CoMSIA methodologies. The statistical results of CoMFA (A5: $r^2\;_{cv.}\;=\;0.707\;&\;r^2\;_{ncv.}$= 0.986) and CoMSIA model (A3: $r^2\;_{cv.}$ = 0.715 & $r^2\;_{ncv.}$ = 0.961) showed the best predictability and fitness for neuroblocking activity based on the cross-validated value and non-cross validated value. The steric and H-bond acceptor nature of a compound were essential for high activity. The study on 3D-QSARs between substrate molecules and their neuroblocking activities appears to be an useful approach for designing better neuroblocking drug development.

• Annals of Clinical Neurophysiology
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• v.9 no.2
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• pp.51-58
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• 2007

Autoimmune myasthenia gravis (MG) is the neuromuscular junction disorder mostly caused by antibody against the acetylcholine receptor (AChR antibody) at the muscle endplate. The goal of treatment is to induce and maintain remission, i.e., absence of symptoms, with the least cost-to-benefit ratio. Although corticosteroids are effective in inducing remission in most patients, they have numerous potentially serious adverse effects with their long-term use. In addition, some patients do not respond or are intolerant to the conventional treatment. In this article, we discuss the difficulties encountered in long-term immunosuppressive treatment of MG, and review useful tips for the use of corticosteroids. Long-term immunosuppressive agents that can be used in steroid-refractory or -dependent patients will be reviewed with their safety profiles and efficacy in MG.

• Biomolecules & Therapeutics
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• v.9 no.2
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• pp.119-124
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• 2001

In order to determine the role of dehydroepiandrosterone (DHEA), the important sex-steroid hormone precursor, in vascular reactivity in rats, animals were treated for two weeks with DHEA or sex hormones, and the vascorelaxant and contractile responses of isolated aorta were examined. DHEA diminished the acetylcholine (ACh)-induced relaxation in female rats, while the drug was without effect in males. Testoterone lowered the vasorelaxant activity to ACh in either sex. 17$\beta$-Estradiol enhanced ACh-induced vasorelaxation in male rats, but this female sex hormone did not influence in females. In male rats, the androgen receptor antagonist flutamide also enhanced vasorelaxant action of ACh. When the male rat aorta was incubated in vitro with a nitric oxide (NO) synthase inhibitor L-NAME, phenylephrine-induced contraction was greatly potentiated in DHEA-pretreated rats compared to control ones. The present results suggest that DHEA stimulates mainly androgen in female, but both androgen and estrogen in male rats. The participation of NO In the modulation of vascular reactivity with pretreated DHEA was also considered.

• The Korean Journal of Food And Nutrition
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• v.34 no.5
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• pp.545-552
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• 2021

HAE-06 extract is a mixture of four medicinal plants, namely Lonicerae Folium et Caulis (Lonicera japonica), Scutellariae Radix (Scutellaria baicalensis), Adenophorae Radix (Adenophora triphylla var. japonica), and Polygonati Oddorati Rhizoma (Polygonatum odoratum var. pluriflorum). The HAE-06 extract demonstrated a concentration-dependent relaxing effect and enhanced cAMP production in bronchial smooth muscle that had been stimulated to contract with acetylcholine. Using a blocker, it was confirmed that the effect was through the β2-adrenergic receptor/cAMP/PKA pathway. In addition, it is thought that the HAE-06 extract has a bronchial smooth muscle relaxation effect by reducing the inflow of Ca²⁺ through the K⁺ and Ca²⁺ channels present in the sarcoplasmic membrane. If research continues in the future, it is believed that it will be possible to use it as a material for pharmaceuticals and functional foods.

• Korean Journal of Biological Psychiatry
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• v.8 no.1
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• pp.62-70
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• 2001

Alzheimer's disease(AD) is associated with a characteristic neuropathology. The major hallmarks of AD are senile plaques (SPs) and neurofibrillary tangles(NFTs). ${\beta}$-amyloid protein($A{\beta}$) is derived from the proteolysis of amyloid precursor protein(APP) and then converted to SPs. Mature SPs produce cytotoxicity through direct toxic effects and activation of microglia and complement. NFTs are composed of paired helical filaments(PHFs) including abnormally phosphorylated form of the microtubule-associated protein(MAP) tau and increased tau level in cerebrospinal fluid may be observed in most AD. The aggregation of $A{\beta}$ and tau formation are thought to be a final common pathway of AD. Acetylcholine, dopamine, serotonin, GABA and their receptors are associated with AD. Especially, decreased nicotinic acetylcholine receptors(nAChRs) in AD are reported. Genetic lesions associated with AD are mutations in the structural genes for the APP located on chromosome 21, presenilin(PSN)1 located on chromosome 14 and PSN2 located on chromosome 1. Also, trisomy 21, Apo-E gene located on chromosome 19, PMF locus, low density lipoprotein receptor-related protein and ${\alpha}$-macroglobulin increase risk of AD. In this article, we will review about the neurobiology of AD and some newly developed research areas.

• Biomolecules & Therapeutics
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• v.13 no.1
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• pp.26-31
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• 2005

The present study examined effects of a water-soluble fraction from mulberry leaves (ML water fraction) on the circulatory and autonomic nervous systems, which were compared with those of acetylcholine (ACh) used as a reference drug in order to elucidate its mechanism of action. Intravenous administration of ACh or a ML water fraction produced temporary depressor and tachycardiac responses in a dose-dependent manner in unrestrained, conscious Sprague-Dawley rats. The systemic hemodynamic effects of ACh and a ML water fraction were almost completely blocked by pretreatment with atropine, a muscarinic antagonist. The depressor responses to ACh and a ML water fraction were slightly enhanced and prolonged by pretreatment with neostigmine, an anticholinesterase, whereas the tachycardiac responses were remarkably blocked by pretreatment with pentolinium, a ganglionic blocking agent. In vitro experiments using the ileum isolated from rats showed that ACh and a ML water fraction increased ileal contractility in a dose-dependent manner. The increases in ileal contractility were also completely abolished in the presence of atropine. Finally, the specific binding of [$^3H$]quinuclidinyl benzilate, a muscarinic antagonist, to rat cortical synaptic membranes was inhibited by a ML water fraction in a concentration-dependent manner with an IC$_{50}$ value of 9.5 mg/ml. The results suggest that the effects of a ML water fraction are mediated through direct stimulation of muscarinic cholinergic receptors by unknown cholinomimetic substance(s) contained in that fraction.

• The Korean Journal of Physiology
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• v.26 no.2
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• pp.129-136
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• 1992

The effects of $Cd^{2+}$ on spontaneous contraction, and the contractures induced by $0mM\;Na^+,\;60mM\;K^+\;and\;10^{-6}\;M$ acetylcholine, 1mM caffeine were studied in order to elucidate diverse actions of $Cd^{2+}$ on the $Ca^{2+}$ mobilization related with contractility in the antral circular muscle of guinea pig stomach. $Cd^{2+}$ inhibited the spontaneous contraction in a does dependent manner $(10^{-6}\;M\;10^{-4}\;M).\;Cd^{2+}\;(3{\times}10^{-5}M)$ suppressed 60 mM $K^+$ induced contracture composed or a phasic and a tonic response and the increased tonic response by the increased external $Ca^{2+}$ concentration. $Cd^{2+}$ also suppressed acetylcholine induced contracture composed of repetitive phasic and a tonic component and the increased tonic response by the increased external $Ca^{2+}$ concentration. Caffeine in the concentration of 1mM evoked contracture but $Cd^{2+}$ suppressed the contracture. $Cd^{2+}$ suppressed the amplitude of the $Na^+$ tee contracture dose dependently and the amplitude of $Na^+$ free contracture almost decreased to 20% of control amplitude in the concentration of $10^{-4}\;M\;Cd^{2+}$. From the above results, it is suggested that $Cd^{2+}$ may inhibit not only $Ca^{2+}$ influx via voltage sensitive, receptor operated $Ca^{2+}$ channel and Na/ca exchange but also intracellular $Ca^{2+}$ release from the sarcoplasmic reticulum in the antral circular muscle of guinea pig stomach.

• Journal of Chest Surgery
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• v.27 no.7
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• pp.610-616
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• 1994

Myasthenia gravis is a rare condition, affecting only 1/75000. It is characterized by weakness and fatigue of the voluntary muscles due to impaired neuromuscular transmission at the acetylcholine receptor site. It is probably caused by an autoimmune mechanism leading to reduction of the available nicotinic acetylcholine receptors at the neuromuscular junction. A relationship between the thymus and myasthenia gravis was suggested by Weigert in 1901, and Blalock was the first to report the efficiency of thymectomy in the treatment of myasthnia gravis in 1939. Since that time, thymectomy has become increasingly important in managing patients with myasthenia gravis. Fourteen patients with myasthenia gravis underwent thymectomy between September 1987 and March 1994 and got the following results; 1. The sex distribution was 10 females and 4 males with ages ranging from 15 to 51 years[mean, 34.8 years]. 2. Clinical manifestation of ocular symptoms were seen in all cases, dysphagia in 12[85.7%], extremity weakness in 11 [78.6 %], and dyspnea in 3 [21.4 %]. 3. According to the modified Osserman`s classification, 8 patients were in group IIb, 3 in IIa, 2 in I and 1 in IIc, respectively. 4. Histopathologic examination of the resected thymuses revealed hyperplasia in 8 patients, benign thymoma in 3, and malignant thymoma in 3. 5. There were no perioperative or immediate postoperative deaths but one patient died about two months after the thymectomy due to respiratory failure. 6. During the follow-up period, 11 patients [78.6 %] showed clinical improvement. Among them, 4 cases [28.6 %] showed complete remission, 3 [21.4 %] showed marked improvement, and 4 [28.6 %] showed subjective improvement. 7. Among the 8 patients with thymic hyperplasia, clinical improvement was noticed in 7 patients 5 %]. Among the 6 patients with thymoma, 4 patients [66.7 %] showed improvement.