中文摘要
已有很多報導顯示Sigma-1作用劑有抗失憶的作用尤其是改善p-chloroamphetamine ( 5-HT釋放劑)，dizocilpine ( glutamate NMDA 接受器離子通道的阻斷劑)或scopolamine (乙醯膽鹼接受器拮抗劑)等引致之失憶。因此，我們使用ICR小鼠腦部細胞膜樣品建立sigma- 1接受器結合性試驗來評估十二種中藥水抽提物是否對sigma-1接受器有相互作用。結果發現十二種中藥水抽提物皆對sigma-1接受器有親和力，其親和力大小範圍從黃連之Ki=1.85x10-3 mg/ml至柴胡之Ki= 5.21 mg/ml。以適用ICR小鼠之方形水迷宮置放學習模式來評估這些中藥是否也都具有抗失憶的效果，結果發現大棗(1.5-3.0 g/kg, i.p.)、香附(3.5-5.0 g/kg, i.p.)、石菖蒲(0.5-1.5 g/kg, i.p.)在scopolamine (8.0 mg/kg, i.p.)前10分鐘預處理與只給scopolamine比較，在記憶測試時會減少游到平台區域的時間並且會增加停留在平台區域的時間，即具有抗失憶作用。為了檢驗這些中藥之抗失憶作用是否與sigma-1接受器活化有關，我們使用sigma-1拮抗劑haloperidol (0.25 mg/kg, i.p.)與這些中藥同時注射來評估。結果顯示haloperidol可以逆轉sigma-1作用劑SKF-10047 (3.0 mg/kg, i.p.)所產生的抗失憶作用但卻對大棗、香附、石菖蒲所產生的抗失憶作用，沒有明顯的影響。因此可知大棗、香附、石菖蒲的抗失憶作用並非經由sigma-1接受器媒介。相對地，於所測試中藥中對於sigma-1接受器具有最高親和力之黃連，在0.1 mg/kg下可以逆轉由SKF-10047所產生的抗失憶作用，所以黃連具有像sigma-1拮抗劑的作用。

英文摘要
Many studies have shown that sigma-1 receptor agonists exert potent antiamnesic effects by improving learning and memory impairments induced by p-chloroamphetamine (a 5-HT releaser), dizocilpine (a glutamate NMDA receptor channel blocker), or scopolamine (a muscarinic acetylcholine receptor antagonist). To evaluate whether the water extracts from 12 Chinese herbal drugs can interact with the sigma-1 receptors, a sigma-1 receptor binding assay using mice brain membrane preparations was established and used. The results indicated that these water extracts all interacted with the sigma-1 receptors with different affinities ranging from Huanglian (Ki=1.85x10-3 mg/ml) to Chaihu (Ki=5.21 mg/ml). To evaluate whether they have antiamnesic effects, this study used placing learning in a rectangular water maze adapted for mice. As compared with scopolamine alone, Dazao (1.5-3.0 g/kg, i.p.), Xiangfu (3.5-5.0 g/kg, i.p.), or Shichangpu (0.5-1.5 g/kg, i.p.) administrating 10 min before scopolamine (8.0 mg/kg, i.p.) increased the latency to reach the platform location and decreased the time spent within the platform location at the retention test session. To test whether an activation of sigma-1 receptors is involved in their antiamnesic effects, a sigma-1 receptor antagonist haloperidol (0.25 mg/kg, i.p.) was co-administered with the test Chinese drug. Haloperidol was able to reverse the antiamnesic effect of a sigma-1 receptor agonist SKF-10047 (3.0 mg/kg, i.p.) but had no significant effect on Dazao, Xiangfu, or Shichangpu. Therefore, these results indicated that the antiamnesic effects of Dazao, Xiangfu, and Shichangpu are not via sigma-1 receptors. In contrast, Huanglian (0.1 mg/kg, i.p.), having the highest affinity for the sigma-1 receptor among the test Chinese herbal drugs, was able to reverse the antiamnesic effect of SKF-10047. Therefore, Huanglian acts like a sigma-1 receptor antagoinist.

目錄
中文摘要
英文摘要
緒 論…………………………………………………………………1
研究目的…………………………………………………………………7
實驗材料及方法………………………………………………………..16
一.實驗動物與藥品試劑之來源………………………………...16
1.動物………………………………………………………..16
2.實驗藥品與試劑…………………………………………..16
3.中藥的來源與水抽提物備…………………………….….17
二.實驗方法……………………………………………………...17
1.接受器結合驗………………………………………….….17
2.水迷宮之空間記憶實驗…………………………………..20
三. 統計方法……………………………………………………...21
實驗結果………………………………………………………………..22
一. Sigma-1接受器結合性實驗………………………………….22
二. 水迷宮測試之建立…………………………………………...22
三. 中藥水抽取物之抗失憶作用………………………………...24
1.柴 胡……………………………………………………....24
2.香 附………………………………………………………24
3.大 棗………………………………………………………25
4.木 通………………………………………………………26
5.遠 志………………………………………………………26
6.黃 連………………………………………………………27
7.徐長卿……………………………………………………..28
8.單 參………………………………………………………28
9.玄 參………………………………………………………29
10.地骨皮……………………………………………………..29
11.蛇床子……………………………………………………..30
12.石菖蒲……………………………………………………..31
四. Haloperidol之拮抗……………..…………………………….31
五. 黃連對SKF-10047之拮抗……..…………………………….32
六. Berberine對SKF-10047之拮抗……………………………32
討 論………………………………………………………………..33
參考文獻………………………………………………………………..41
圖 表………………………………………………………………..51

參考文獻
張伯萸、董建華、周仲瑛 (1989) 中醫內科學。知音出版社，台北
顏焜熒 (1996) 原色生藥學第二版。南天書局有限公司，台北
陳建軍、黃青鬆、趙學軍 (1998) 腦力康對老齡小鼠空間分辨學習和記憶的影響。安徽中醫學院學報 17(2): 63-64.
Bell, J.A., Spivak, C.E., Su, T.P., London, E.D. (1988) Haloperidol — sensitive, selective electrophysiological effects of sigma ligands on NCB-20 cell. Soc. Neurosci. Abstr. 14:1155.
Beveniste, H., Drejer, J., Schousboue, A., Diemer, N.H. (1984) Elevation of the extracellular contrations of glutamate and aspartate in rat hippocampus during transient cerebral ischemia monitored by intracerebral microdialysis. J. Neurochem. 43:1369-1374.
Borowicz, K.K., Wilczy'' nski, P.M., Kleinrok, Z., Czuczwar, S.J. (1998) Rimcazole, a sigma receptor ligand, and the anticonvulsive action of conventional antiepileptic drug. J. Neurol. Transm. 105:601-612.
Bradford, M.M. (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 72:248-254.
Cahusac, P.M., Miyashita, Y., Rolls, E.T. (1989) Responses of hippocampal formation neurons in the monkey related to delayed spatial response and object-place memory tasks. Behavioural Brain Res. 33(3):229-40.
Campbell, B.G., Scherz, M., Keana, J.F.W., Weber, E. (1989) Sigma receptors inhibit contractions of the guinea pig ileum longitudinal muscle/myenteric plexus preparation elicted by both electrical stimulation and exogenous serotonin. J. Neurosci. 9:3380-3391.
Casellas, P., Bourrie, B., Canat, X., Carayon, P., Buiaaon, I., Paul, R., Breliere, J.C., Fur, G.L. (1994) Immunopharmacological profile of SR 31747: in vitro and in vivo studies on humoral and cellular responses. J. Neuroimmunol. 52:193-203.
Cheng, Y.C., Prusoff, W.H. (1973) Relationship between the inhibition constant and the concentration of inhibitor which cause 50% inhibition of an emzymatic reaction. Biochem. Pharmacol. 22:3099-3018.
Choi, D.W., Koh, J.Y., Peters, S. (1988) Pharmacology of glutamate neurotoxicity in cortical cell culture: Attenuation by NMDA antagonists. J. Neurosci. 8:185-196.
Choi, D.W., Peters, S., Viseskul, V. (1987) Dextrorphan and levorphenol selectively block NMDA receptor-mediated neurotoxicity on cortical neurons. J. Pharmacol. Exp. Ther. 242:713-720.
Chou, Y.C., Laio, J.F., Chang, W.Y., Lin, M.F., Chen, C.F. (1999) Binding of dimemorfan to sigma-1 receptor and its anticonvulsant and locomotor effects in mice, compared with dextromethorphan and dextrophan. Brain Res. 821:516-519.
Christina, G., Benishin, Raymond, L., Lawrene, C.H., Wang, Hsin, J.L. (1991) Effects of ginsenoside Rb1 on central cholinergic metabolism. Pharmacology 42:223-229.
Contras, P.C., Gray, N.M., Ragan, D.A., Lanthorn, T.H. (1992) BMY-14802 protects against ischemia-induced neuronal damage in the gerbil. Life Sci. 51:1143-1151.
Cook, L., Tam, S.W., Rohrbach, K.W. (1992) Du 734 [1-(cyclo propyl- methyl)-4-(2’(4’’fluorophenyl)-2’-oxoethyl)piperidine Hbr], a potential antipsychotic agent: Preclinical behavioral effects J. Pharmacol. Exp. Ther. 263:1159-1166.
Culp, S.G., Rominger, D., Tam, W.S., De Sourza, E.B. (1992) [3H]Du 734 [1-(cyclopropyl-methyl)-4-(2’(4’’fluorophenyl)-2’-oxoethyl) piperidine Hbr]: A receptor binding profile of a high affinity novel sigma receptor ligand in guinea pig brain. J. Pharmacol. Exp. Ther. 263:1175-1187.
Day, J.C., Fibiger, H.C. (1994) Dopaminergic regulation of septohippocampal cholinergic neurons. J. Neurochem. 63:2086-2092.
Den Boer, J.A., Ravelli, D.P., Huisman, J., Ohrvik, J., Verhoeven, W.M.A., Westenberg, H.G.M. (1990) Double blind comparative study of remoxipride and haloperidol in schizophrenic patients. Psychopharmacology 102:76-84.
Drejer, J., Benveniste, H., Diemer, N.H., Schousboe, A. (1985) Celler origin of ischaemic-induced glutamate release from brain tissue in vivo and in vitro. J. Neurochem. 45:145-151.
Earley, B., Bueke, M., Leonard, B.E., Gouret, C.J., Junien, J.L. (1991) Evidence for an anti-amnesic effect of JO-1784 in the rat: a potent and selective ligand for the sigma receptor. Brain Res. 546:282-286
Fujji, T., Yoshizawa, M., Nakai, K., Fulimoto, K., Suzuki., T., Kawashima, K. (1997) Demonstration of the facilitatory role of 8-OH- DPAT on cholinergic transmission in the rat hippocampus using in vivo microdialysis. Rain Res. 761:244-249.
Gao, C.R., Zhang, J.O., Huang, Q.L. (1997) Experimental study on berberin raised insulin sensitivity in insulin resistance rat models . Chung-Kuo Chung Hsi i Chieh Ho Tsa Chih. 17(3):162-164.
Gilbert, P.E., Martin, W.R. (1976) Sigma effects of nalorphine in the chronic spinal dog. J. Drug Alcohol Depend. 1:373-376.
Glick, S.D., and Zimmerberg, B. (1972) Amnesic effects of scopolamine. Behav. Biol. 7:245-254.
Graybiel, A.M., Besson, M.J., Weber, E. (1989) Neuroleptic-sensitive binding sites in the nigrostriatal system: Evidence for differential distrubition of sigma sites in the substantia nigra, pars compacta of the cat. J. Neurosci. 9:326-338.
Gronier, B., Debonnel, G. (1999) Involvement of sigma receptors in the modulation of the glutamatergic/NMDA neurotransmission in the dopaminergic systems. Eur. J. Pharmacol. 368:183-196.
Jin, S.H., Park, J.K., Nam, K.Y., Park, S.N., Jung, N.P. (1999) Korean red ginseng saponins improve scopolamine-induced learning disability and spital working memory in mice. 66(2):123-129.
Juine, J.L., Gue, M., Bueno, L. (1991) Neuropeptide-Y and sigma-ligand (JO 1784) act through a Gi protein to block the psychological stress and corticotropin releasing factor-induced colonic motor activation in rats. Neuropharmacology 30:1119-1124.
Junien, J.L., Roman, F.J., Brunelle, G., Pascaud, X. (1991) JO-1784, a novel sigma ligand, potentiates [3H]acetylcholine release from rat hippocampal slices. Eur. J. Pharmacol. 200:343-345.
Kamei, J., Iwamoto, Y., Kawashima, N., Hitosugi, H., Misawa, M., Kasuya, Y. (1992) Involovement of haloperidol-sensitive sigma-sites in antitussive effects. Eur. J. Pharmacol. 224:39-43.
Kim, H.M., Lee, E.H., Na, H.J., Lee, S.B., Shin, T.Y., Lyu, Y.S., Kim, N.S., Nomura, S. (1998) Effect of Polygala tenuifolia root extract on the tumor necrosis factor-alpha secretion from mouse astrocytes. J. Ethnopharmacol. 61(3):201-208.
Ko, W.H., Yao, X.Q., Lau, C.W., Law, W.I., Chen, Z.Y. Kwok, W., Ho, K., Huang, Y. (2000) Vasorelaxant and antiproliferative effects of berberine. Eur. J. Pharmacol. 399(2-3):187-196, 2000.
Lamberty, Y., Gower A.J. (1991) Cholinergic modulation of spatial learning in mice in a Morris-type water maze. Arch. Int. Pharmacodyn. 309:5-19.
Levant, B., Nemeroff, C.B. (1990) Sigma receptor "antagoinsts" BMY 14802 increases neurotensin concentrations in the rat nucleus accumbens and caudate. J. Pharmacol. Exp. Ther. 254:330-335.
Levin, E.D., Simon, B.B. (1998) Nicotinic acetycholine involvement in cognitive function in animals. Psychopharmacology 138:217-230.
Liao, J.F., Huang, S.Y., Jan, Y.M., Yu, L.L., Chen, C.F. (1998) Central inhibitory effects of water extract of Acori graminei rhizoma in mice. J. Enthopharmacol. 61(3):185-193.
Liao, J.M., Zhu, Q.A., Lu, H.J., Li, Q.N., Wu, T., Huang, L.F. (1997) Effects of total coumarins of Cnidium monnieri on bone density and biomechanics of glucocorticoids-induced osteoporosis in rats. Chung-Kuo Yao Li Hsueh Pao - Acta Pharmacologica Sinica. 18(6): 519-521.
Liu, G.Q., Sun, J.N., He, Z.Z., Jiang, Y. (1983) Spasmolytic actions of active principles of volatile oil of Acorus gramineus. Chung-Kuo Yao Li Hsueh Pao - Acta Pharmacologica Sinica. 4(2):95-97.
Lozovsky, D., Saller, C.F., Bayorh, M.A., Chiueh, C.C., Rice, K.C., Burke, Jr., Kopin, I.J. (1983) Effects of phencyclidine on rat prolactin, dopamine receptor and locomotor activity. Life Sci. 32:2725-2731.
Martin, W.R., Eades, C.G., Thompson, J.A., Huppler, R.E., Gilbert, P.E. (1976) The effects of morphine and nalorphine-like drugs in the non-dependent and morphine-dependent chronic spinal dog. J. Pharmacol. Exp. Ther. 197:517-532.
Mash, D.C., Zabetian, C.P. (1992) Sigma receptors are associated with cortical limbic areas in the primate brain. Synapse 12:195-205.
Matsuno, K., Matsunaga, K., Mita, S. (1992) Increase of extracellular acetylcholine level in rat frontal cortex induced by (+)N-allylnormetazocine as measured by brain microdialysis. Brain Res. 575:315-319.
Matsuno, K., Matsunaga, K., Senda, T., Mita, S. (1993a) Increase in extracellular acetylcholine level by sigma ligands in rat frontal cortex. J. Pharmacol. Exp. Ther. 265:851-859.
Matsuno, K., Senda, T., Kobayashi, T., Mita, S. (1995) Involvenent of sigma-1 receptor in (+)-N-allylnormetazocine-stimulated hippocampal cholinergic function in rats. Brain Res. 690:200-206.
Matsuno, K., Senda, T., Kobayashi,T., Okamoto, K., Nakata, K., Mita, S. (1997) SA4503,a novel cognitive enhancer, with sigma-1 receptor agonistic properties. Behav. Brain Res. 83:221-224.
Matsuno, K., Senda, T., Matsunaga, K., Mita, S. (1994b) Ameliorating effects of sigma receptor ligands on the impairment of passive avoidance task in mice: Involvement in the central acetylcholinergic system. Eur. J. Pharmacol. 261:43-51.
Matsuno, K., Senda, T., Matsunaga, K., Mita, S., Kaneto, H. (1993b) Similar ameliorating effects of benzorphans and 5-HT2 antagonists and drug-inducd impairment of passive avoidance response in mice: comparison with acetylcholinesterase inhibitor. Psychopharmacology 112:134-141.
Maurice, T., Hiramatsu, M., Itoh, J., Kameyama, T., Hasegawa T., Nabeshima, T. (1994a) Behavioral evidence for a modulating role of sigma ligands in memory processes. I. Attenuation of dizocipline (MK-801)-induced amnesia. Brain Res. 647:44-56.
Maurice, T., Hiramatsu, M., Itoh, J., Kameyama, T., Hasegawa T., Nabeshima, T. (1994b) Low dose of 1,3-di(2-tolyl)guanidine (DTG) attenuates MK-801-induced spital working memory impairment in mice. Psychopharmacology 114:520-522.
Maurice, T., Junien, J.L., Privat, A. (1997) Dehydroepiandrosterone sulfate attenuates dizocilpine-induced learning impairment in mice via sigma-1 receptors. Behav. Brain Res. 83:159-164.
Maurice, T., Roman, F.J., Privat, A. (1996) Modulation by neurosteroids of the in vivo (+)-[3H]SKF-10047 binding to sigma-1 receptors in the mouse forebrain. J. Neurosci. Res. 46:734-743.
Maurice, T., Roman, F.J., Su, T.P., Privat, A. (1996) Benefical effects of sigma agoinsts on the age-realated learning impairment in the senescence-accelerated mouse (SAM). Brain Res. 733:219-230.
McGurk, S.R., Levin, E.D., Butcher, L.L. (1992) Dopaminergic drugs reverse the impairment of radial-arm maze performance caused by lesions involoving the cholinergic medial pathway. Neurosci. 50(1):129-135.
McLean, S., Weber, E. (1988) Autoradiographic visualization of haloperidol-sensitive sigma receptors in guinea-pig brain. Neuro- scinence 25:259-269.
MiItoh, T., Michijiri, S., Murai, S., Saito, H., Saito, H., Itsukaichi, O., Fujiwara, H. (1996) Effects of chaihu-guizhi-ganjiang-tang on the levels of monoamines and their related substances, and acetylcholine in discrete brain regions of mice. Am. J. Chinese Med. 24(1):53-64.
Moebius, F.F., Hanner, M., Knaus, H.G., Weber, F., Striessnig, J., Glossmann, H. (1994) Purification and amino-terminal sequencing of the high affinity phenylalkylamine Ca2+ antagonist binding protein from guinea pig liver endoplasmic reticulum. J. Biol. Chem. 269:29314-29320.
Monnet, F.P., Debonnel, G., De Montigny, C. (1991) The modulation by sigma ligands of NMDA-evoked [3H]noradrenaline release involove Gi/o protein. Soc. Neurosci. Abstr. 17:1340-1342.
Monnet, F.P., Debonnel, G., Junien, J.L., De Montigny, C. (1990) N-methyl-D-aspartate-induced neuronal activation is selectively modulated by sigma receptors. Eur. J. Pharmacol. 179:441-445.
Ohno, M. and Watanabe, S. (1995) Intrahippocampal administration of (+)-SKF-10047, a sigma ligand, reverses MK-801-induced impairment of working memory in rats. Brain Res. 498:195-198.
Pascaud, X., Chovet, M., Roze, C., Junien, J.L. (1993) Neuropeptide Y and sigma receptor agonists act through a common pathay to stimulate duodenal alkaline secretion in rats. Eur. J. Pharmacol. 231:389-394.
Pascaud, X., Defaux, J.P., Roze, C., Junien, J.L. (1990) Effect of selective sigma ligands on duodenal alkaline secretion in the rat. J. Pharmacol. Exp. Ther. 255:1354-1359.
Pechnick, R.N., George, R., Lee, R.J., Poland, R.E. (1986) The effects of the acute administration of phencyclidine hydrochloride (PCP) on the release of corticosterone, growth hormone and prolactin in the rat. Life Sci. 38:291-296.
Pechnick, R.N., George, R., Poland, R.E. (1985) Identification of multiple opiate receptors through neuroendocrine responses. I. effects of agoinsts. J. Pharmacol. Exp. Ther. 232:163-169.
Pontecorvo, M.J., Karbon, E.W., Goode, S., Clissold, D.B., Borodsky, S.A., Patch, R.J., Ferkany, J.W. (1991) Possible cerebroprotective and in vivo NMDA antagoinist activities of sigma agents. Brain Res. Bull. 26:461-465.
Quirion, R., Chicheportiche, R., Contreras, P.C., Johnson, K.M., Lodge, D., Tam, S.W., Woods, I.H., Zukin, S.R. (1987) Classification and nomenclature of phencyclidine and sigma receptor sites. Trends Pharmacol. Sci. 10:444-446.
Rhodes, M.J., Price, K.R. (1997) Identification and analysis of plant phenolic antioxidants. Eur. J. Cancer Prevent. 6(6):518-521.
Rogers, C., Lemaire, S. (1991) Role of the sigma receptor in the [3H]noradrenaline uptake in brain synaptosomes and adrenal chromaffin cell. Br. J. Pharmacol. 103:1917-1922.
Roman, F., Pascaud, X., Chomette, G., Bueno, Junien, J.L. (1989) Autoradiographic localization of sigma opioid receptors in the gastrointestinal tract of guinea pig. Gastroenterology 97:76-82.
Ross, S.B. (1991) Heterogeneous binding of sigma radioligands in the rat brain and liver: Possible relationship to subforms of cytochrome P-450. Pharmacol. Toxicol. 68:293-301.
Saller, C.F., Zerbe, R.L., Bayorh, M.A., Lozovsky, D., Kopin, I. (1982) Phencyclidine supresses plasma prolactin levels. Eur. J. Pharmacol. 83:309-311.
Samovilova, N.N., Nagornaya, L.V., Vinogradov, V.A. (1988) (+)-[3H]- SKF10047 binding sites in rat liver. Eur. J. Pharmacol. 165:335-336.
Sarter, M., Bodewitz, G., David, N.D. (1988) Attenuation of scopolamine-induced impairment of spontaneous alternation behaviour by antagoinst but not inverse agonist and agonist b-carbolines. Psychopharmacology 94:491-495.
Schuster, D.I., Ehrlich, G.K., Murphy, R.B. (1994) Purification and partial amino acid sequence of a 28kDa cyclophiline-like component of the rat liver sigma receptor. Life Sci. 55:151-156.
Stojilkovic, S., Dufau, M., Catt, K. (1987) Opiate receptor subtypes in the rat hypothalamus and neurointermediate lobe. Endocrinology 121:384-394.
Su, T.P. (1991) Sigma receptors: Putative links between nerves, endocrine and immune systems. Eur. J. Biochem. 200:633-642.
Taylor, D.P., Dekleva, J. (1987) Potential antipsychotic BMY-14802 selectively binds to sigma sites. Drug Dev. Res. 11:65-70.
Ujike, H., Tsuchida, K., Akiyama, K., Otsuki, S. (1992) Supersensitivity of sigma receptors after repeated administeration of cocaine. Life Sci. 50:1673-1681.
Urani, A., Privat, A., Maurice, T. (1998) The modulation by neurosteroids of the scopolamine-induced learning impairment in mice involves an interaction with sigma1 receptors. Brain Res. 799(1):64-77.
Walker, J.M., Matsumoto, R.R., Bowen, W.D., Gan, D.L., Jone, K.D., Walker, F.O. (1988) Evidence for a role of haloperidol-sensitive sigma-1 opiate receptors in the motor effects of antipsychotics drugs. Neurology 38:961-965.
Wang, B.S., Wang, L.J., Zhang, Y.B., Lu, J.S., Tang, N., Huang, Y.T., Yan W.H., Song, W. (1997) Reduction of myocardial ischemia-reperfusion injury by isovolumic hemodilution. Clin. Hemorheol. Microcircul. 17(3):181-186.
Wolfe, Jr., S.A., Culp, S.G., De Souza, E. B. (1989) Sigma receptors in endocrine organs: identification, charactization, and autoradiographic location in rat pituitary, adrenal, testis and ovary. Endocrinology 124:1160-1172.
Wolfe, J., Kulsakdinun, C., Battaglia, G., Jaffe, J.J., De Souza, E.B. (1988) Intial identification and characterization of sigma receptors on human peripheral blood leukocyte. J. Pharmacol. Exp. Ther. 247:1114-1119.
Wu, X.Z., Bell, J.A., Spivak, C.E., London, E.D., Su, T.P. (1991) Electrophysiological and binding studies on intact NCB-20 cells suggest presence of a low affinity sigma receptor. J. Pharmacol. Exp. Ther. 257:351-359.
Yang, C.S., Lin, C.H., Chang, S.H., Hsu, H.C. (2000) Rapidly progressive fibrosing interstitial nephritis associated with Chinese herbal drugs. Am. J. Kidney Dis. 35(2):313-318.
Yang, C.R., Mogenson, G.J. (1990) Dopaminergic modulation of cholinergic responses in rat medial prefrontal cortex: an electrophysiological study. Brain Res. 524(2):271-281.
Yu, C.M., Chan, J.C., Sanderson, J.E. (1997) Chinese herbs and warfarin potentiation by danshen. J. Internal Med. 241(4):337-339.