{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T19:19:58Z","timestamp":1791141598801,"version":"4.1.0"},"reference-count":39,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2010,3,2]],"date-time":"2010-03-02T00:00:00Z","timestamp":1267488000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["BMC Pharmacol"],"published-print":{"date-parts":[[2010,12]]},"DOI":"10.1186\/1471-2210-10-3","type":"journal-article","created":{"date-parts":[[2010,3,2]],"date-time":"2010-03-02T19:16:21Z","timestamp":1267557381000},"source":"Crossref","is-referenced-by-count":31,"title":["Targeting ligand-gated ion channels in neurology and psychiatry: is pharmacological promiscuity an obstacle or an opportunity?"],"prefix":"10.1186","volume":"10","author":[{"given":"Matt T","family":"Bianchi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel J","family":"Botzolakis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2010,3,2]]},"reference":[{"issue":"1","key":"716_CR1","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1038\/sj.embor.7401147","volume":"9","author":"F Mazzocchi","year":"2008","unstructured":"Mazzocchi F: Complexity in biology. Exceeding the limits of reductionism and determinism using complexity theory. EMBO Rep. 2008, 9 (1): 10-14. 10.1038\/sj.embor.7401147.","journal-title":"EMBO Rep"},{"issue":"2","key":"716_CR2","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1038\/nbt1519","volume":"27","author":"I Nobeli","year":"2009","unstructured":"Nobeli I, Favia AD, Thornton JM: Protein promiscuity and its implications for biotechnology. Nat Biotechnol. 2009, 27 (2): 157-167. 10.1038\/nbt1519.","journal-title":"Nat Biotechnol"},{"issue":"8","key":"716_CR3","doi-asserted-by":"publisher","first-page":"683","DOI":"10.1002\/(SICI)1521-1878(199808)20:8<683::AID-BIES12>3.0.CO;2-V","volume":"20","author":"RP Erickson","year":"1998","unstructured":"Erickson RP: From \"magic bullet\" to \"specially engineered shotgun loads\": the new genetics and the need for individualized pharmacotherapy. Bioessays. 1998, 20 (8): 683-685. 10.1002\/(SICI)1521-1878(199808)20:8<683::AID-BIES12>3.0.CO;2-V.","journal-title":"Bioessays"},{"issue":"4","key":"716_CR4","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1038\/nrd1346","volume":"3","author":"BL Roth","year":"2004","unstructured":"Roth BL, Sheffler DJ, Kroeze WK: Magic shotguns versus magic bullets: selectively non-selective drugs for mood disorders and schizophrenia. Nat Rev Drug Discov. 2004, 3 (4): 353-359. 10.1038\/nrd1346.","journal-title":"Nat Rev Drug Discov"},{"issue":"7270","key":"716_CR5","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1038\/nature08506","volume":"462","author":"MJ Keiser","year":"2009","unstructured":"Keiser MJ, Setola V, Irwin JJ, Laggner C, Abbas AI, Hufeisen SJ, Jensen NH, Kuijer MB, Matos RC, Tran TB: et al, Predicting new molecular targets for known drugs. Nature. 2009, 462 (7270): 175-181. 10.1038\/nature08506.","journal-title":"Nature"},{"issue":"11","key":"716_CR6","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1038\/nchembio1108-635","volume":"4","author":"RT Peterson","year":"2008","unstructured":"Peterson RT: Chemical biology and the limits of reductionism. Nat Chem Biol. 2008, 4 (11): 635-638. 10.1038\/nchembio1108-635.","journal-title":"Nat Chem Biol"},{"issue":"1","key":"716_CR7","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1186\/1472-6904-5-3","volume":"5","author":"SK Mencher","year":"2005","unstructured":"Mencher SK, Wang LG: Promiscuous drugs compared to selective drugs (promiscuity can be a virtue). BMC Clin Pharmacol. 2005, 5 (1): 3-10.1186\/1472-6904-5-3.","journal-title":"BMC Clin Pharmacol"},{"issue":"4","key":"716_CR8","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1016\/j.tips.2005.02.007","volume":"26","author":"P Csermely","year":"2005","unstructured":"Csermely P, Agoston V, Pongor S: The efficiency of multi-target drugs: the network approach might help drug design. Trends Pharmacol Sci. 2005, 26 (4): 178-182. 10.1016\/j.tips.2005.02.007.","journal-title":"Trends Pharmacol Sci"},{"issue":"295","key":"716_CR9","doi-asserted-by":"publisher","first-page":"pe40","DOI":"10.1126\/stke.2952005pe40","volume":"2005","author":"EE Schadt","year":"2005","unstructured":"Schadt EE, Sachs A, Friend S: Embracing complexity, inching closer to reality. Sci STKE. 2005, 2005 (295): pe40-10.1126\/stke.2952005pe40.","journal-title":"Sci STKE"},{"issue":"5657","key":"716_CR10","doi-asserted-by":"publisher","first-page":"540","DOI":"10.1126\/science.1091403","volume":"303","author":"S Li","year":"2004","unstructured":"Li S, Armstrong CM, Bertin N, Ge H, Milstein S, Boxem M, Vidalain PO, Han JD, Chesneau A, Hao T: et al, A map of the interactome network of the metazoan C. elegans. Science. 2004, 303 (5657): 540-543. 10.1126\/science.1091403.","journal-title":"Science"},{"issue":"7062","key":"716_CR11","doi-asserted-by":"publisher","first-page":"1173","DOI":"10.1038\/nature04209","volume":"437","author":"JF Rual","year":"2005","unstructured":"Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N: et al, Towards a proteome-scale map of the human protein-protein interaction network. Nature. 2005, 437 (7062): 1173-1178. 10.1038\/nature04209.","journal-title":"Nature"},{"issue":"5898","key":"716_CR12","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1126\/science.1158684","volume":"322","author":"H Yu","year":"2008","unstructured":"Yu H, Braun P, Yildirim MA, Lemmens I, Venkatesan K, Sahalie J, Hirozane-Kishikawa T, Gebreab F, Li N, Simonis N: et al, High-quality binary protein interaction map of the yeast interactome network. Science. 2008, 322 (5898): 104-110. 10.1126\/science.1158684.","journal-title":"Science"},{"issue":"4","key":"716_CR13","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1097\/ACO.0b013e32816678a5","volume":"20","author":"K Solt","year":"2007","unstructured":"Solt K, Forman SA: Correlating the clinical actions and molecular mechanisms of general anesthetics. Curr Opin Anaesthesiol. 2007, 20 (4): 300-306. 10.1097\/ACO.0b013e32816678a5.","journal-title":"Curr Opin Anaesthesiol"},{"issue":"5","key":"716_CR14","first-page":"258","volume":"1","author":"RG Eckenhoff","year":"2001","unstructured":"Eckenhoff RG: Promiscuous ligands and attractive cavities: how do the inhaled anesthetics work?. Mol Interv. 2001, 1 (5): 258-268.","journal-title":"Mol Interv"},{"issue":"3","key":"716_CR15","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1016\/j.mehy.2008.09.049","volume":"72","author":"MT Bianchi","year":"2009","unstructured":"Bianchi MT, Pathmanathan J, Cash SS: From ion channels to complex networks: magic bullet versus magic shotgun approaches to anticonvulsant pharmacotherapy. Med Hypotheses. 2009, 72 (3): 297-305. 10.1016\/j.mehy.2008.09.049.","journal-title":"Med Hypotheses"},{"issue":"2","key":"716_CR16","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1016\/j.mehy.2009.09.003","volume":"74","author":"MT Bianchi","year":"2009","unstructured":"Bianchi MT: Promiscuous modulation of ion channels by anti-psychotic and anti-dementia medications. Med Hypotheses. 2009, 74 (2): 297-300. 10.1016\/j.mehy.2009.09.003.","journal-title":"Med Hypotheses"},{"issue":"5","key":"716_CR17","doi-asserted-by":"publisher","first-page":"951","DOI":"10.1016\/j.mehy.2007.09.012","volume":"70","author":"MT Bianchi","year":"2008","unstructured":"Bianchi MT: Non-serotonin anti-depressant actions: direct ion channel modulation by SSRIs and the concept of single agent poly-pharmacy. Med Hypotheses. 2008, 70 (5): 951-956.","journal-title":"Med Hypotheses"},{"issue":"2","key":"716_CR18","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1007\/s12035-007-0006-1","volume":"35","author":"G Rammes","year":"2007","unstructured":"Rammes G, Rupprecht R: Modulation of ligand-gated ion channels by antidepressants and antipsychotics. Mol Neurobiol. 2007, 35 (2): 160-174. 10.1007\/s12035-007-0006-1.","journal-title":"Mol Neurobiol"},{"issue":"10","key":"716_CR19","doi-asserted-by":"publisher","first-page":"1119","DOI":"10.1038\/nbt1338","volume":"25","author":"MA Yildirim","year":"2007","unstructured":"Yildirim MA, Goh KI, Cusick ME, Barabasi AL, Vidal M: Drug-target network. Nat Biotechnol. 2007, 25 (10): 1119-1126. 10.1038\/nbt1338.","journal-title":"Nat Biotechnol"},{"issue":"2-3","key":"716_CR20","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1016\/S0165-0173(98)00052-6","volume":"29","author":"AK Mehta","year":"1999","unstructured":"Mehta AK, Ticku MK: An update on GABAA receptors. Brain Res Brain Res Rev. 1999, 29 (2-3): 196-217. 10.1016\/S0165-0173(98)00052-6.","journal-title":"Brain Res Brain Res Rev"},{"issue":"4","key":"716_CR21","doi-asserted-by":"publisher","first-page":"524","DOI":"10.1016\/j.neuron.2007.12.010","volume":"57","author":"T Lu","year":"2008","unstructured":"Lu T, Rubio ME, Trussell LO: Glycinergic transmission shaped by the corelease of GABA in a mammalian auditory synapse. Neuron. 2008, 57 (4): 524-535. 10.1016\/j.neuron.2007.12.010.","journal-title":"Neuron"},{"issue":"3","key":"716_CR22","doi-asserted-by":"publisher","first-page":"838","DOI":"10.1213\/ane.0b013e31816095bd","volume":"106","author":"L Yang","year":"2008","unstructured":"Yang L, Sonner JM: The anesthetic-like effects of diverse compounds on wild-type and mutant gamma-aminobutyric acid type A and glycine receptors. Anesth Analg. 2008, 106 (3): 838-845. 10.1213\/ane.0b013e31816095bd.","journal-title":"Anesth Analg"},{"issue":"5","key":"716_CR23","doi-asserted-by":"publisher","first-page":"924","DOI":"10.1038\/sj.bjp.0702164","volume":"125","author":"D Colquhoun","year":"1998","unstructured":"Colquhoun D: Binding, gating, affinity and efficacy: the interpretation of structure-activity relationships for agonists and of the effects of mutating receptors. Br J Pharmacol. 1998, 125 (5): 924-947. 10.1038\/sj.bjp.0702164.","journal-title":"Br J Pharmacol"},{"issue":"Pt 3","key":"716_CR24","doi-asserted-by":"publisher","first-page":"769","DOI":"10.1113\/jphysiol.2007.142364","volume":"584","author":"MT Bianchi","year":"2007","unstructured":"Bianchi MT, Botzolakis EJ, Haas KF, Fisher JL, Macdonald RL: Microscopic kinetic determinants of macroscopic currents: insights from coupling and uncoupling of GABAA receptor desensitization and deactivation. J Physiol. 2007, 584 (Pt 3): 769-787. 10.1113\/jphysiol.2007.142364.","journal-title":"J Physiol"},{"issue":"34","key":"716_CR25","doi-asserted-by":"crossref","first-page":"10934","DOI":"10.1523\/JNEUROSCI.23-34-10934.2003","volume":"23","author":"MT Bianchi","year":"2003","unstructured":"Bianchi MT, Macdonald RL: Neurosteroids shift partial agonist activation of GABA(A) receptor channels from low- to high-efficacy gating patterns. J Neurosci. 2003, 23 (34): 10934-10943.","journal-title":"J Neurosci"},{"issue":"4","key":"716_CR26","doi-asserted-by":"publisher","first-page":"988","DOI":"10.1124\/mol.104.002543","volume":"66","author":"HJ Feng","year":"2004","unstructured":"Feng HJ, Bianchi MT, Macdonald RL: Pentobarbital differentially modulates alpha1beta3delta and alpha1beta3gamma2L GABAA receptor currents. Mol Pharmacol. 2004, 66 (4): 988-1003. 10.1124\/mol.104.002543.","journal-title":"Mol Pharmacol"},{"issue":"5","key":"716_CR27","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.1523\/JNEUROSCI.22-05-01541.2002","volume":"22","author":"KM Wohlfarth","year":"2002","unstructured":"Wohlfarth KM, Bianchi MT, Macdonald RL: Enhanced neurosteroid potentiation of ternary GABA(A) receptors containing the delta subunit. J Neurosci. 2002, 22 (5): 1541-1549.","journal-title":"J Neurosci"},{"issue":"6767","key":"716_CR28","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1038\/35002014","volume":"403","author":"F Liu","year":"2000","unstructured":"Liu F, Wan Q, Pristupa ZB, Yu XM, Wang YT, Niznik HB: Direct protein-protein coupling enables cross-talk between dopamine D5 and gamma-aminobutyric acid A receptors. Nature. 2000, 403 (6767): 274-280. 10.1038\/35002014.","journal-title":"Nature"},{"issue":"18","key":"716_CR29","doi-asserted-by":"publisher","first-page":"18840","DOI":"10.1074\/jbc.M313470200","volume":"279","author":"S Balasubramanian","year":"2004","unstructured":"Balasubramanian S, Teissere JA, Raju DV, Hall RA: Hetero-oligomerization between GABAA and GABAB receptors regulates GABAB receptor trafficking. J Biol Chem. 2004, 279 (18): 18840-18850. 10.1074\/jbc.M313470200.","journal-title":"J Biol Chem"},{"issue":"50","key":"716_CR30","doi-asserted-by":"publisher","first-page":"52517","DOI":"10.1074\/jbc.M410223200","volume":"279","author":"E Boue-Grabot","year":"2004","unstructured":"Boue-Grabot E, Toulme E, Emerit MB, Garret M: Subunit-specific coupling between gamma-aminobutyric acid type A and P2X2 receptor channels. J Biol Chem. 2004, 279 (50): 52517-52525. 10.1074\/jbc.M410223200.","journal-title":"J Biol Chem"},{"issue":"9","key":"716_CR31","doi-asserted-by":"publisher","first-page":"732","DOI":"10.1002\/syn.20411","volume":"61","author":"M Miranda-Morales","year":"2007","unstructured":"Miranda-Morales M, Garcia-Hernandez LM, Ochoa-Cortes F, Espinosa-Luna R, Naranjo-Rodriguez EB, Barajas-Lopez C: Cross-talking between 5-HT3 and GABAA receptors in cultured myenteric neurons. Synapse. 2007, 61 (9): 732-740. 10.1002\/syn.20411.","journal-title":"Synapse"},{"issue":"44","key":"716_CR32","doi-asserted-by":"publisher","first-page":"10198","DOI":"10.1523\/JNEUROSCI.2460-05.2005","volume":"25","author":"B Eisensamer","year":"2005","unstructured":"Eisensamer B, Uhr M, Meyr S, Gimpl G, Deiml T, Rammes G, Lambert JJ, Zieglgansberger W, Holsboer F, Rupprecht R: Antidepressants and antipsychotic drugs colocalize with 5-HT3 receptors in raft-like domains. J Neurosci. 2005, 25 (44): 10198-10206. 10.1523\/JNEUROSCI.2460-05.2005.","journal-title":"J Neurosci"},{"issue":"3","key":"716_CR33","doi-asserted-by":"publisher","first-page":"978","DOI":"10.1124\/jpet.102.044834","volume":"304","author":"RT Robinson","year":"2003","unstructured":"Robinson RT, Drafts BC, Fisher JL: Fluoxetine increases GABA(A) receptor activity through a novel modulatory site. J Pharmacol Exp Ther. 2003, 304 (3): 978-984. 10.1124\/jpet.102.044834.","journal-title":"J Pharmacol Exp Ther"},{"issue":"6","key":"716_CR34","doi-asserted-by":"publisher","first-page":"1338","DOI":"10.1016\/j.febslet.2005.01.019","volume":"579","author":"VC Stephenson","year":"2005","unstructured":"Stephenson VC, Heyding RA, Weaver DF: The \"promiscuous drug concept\" with applications to Alzheimer's disease. FEBS Lett. 2005, 579 (6): 1338-1342. 10.1016\/j.febslet.2005.01.019.","journal-title":"FEBS Lett"},{"issue":"5","key":"716_CR35","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1016\/j.conb.2007.11.003","volume":"17","author":"RD Airan","year":"2007","unstructured":"Airan RD, Hu ES, Vijaykumar R, Roy M, Meltzer LA, Deisseroth K: Integration of light-controlled neuronal firing and fast circuit imaging. Curr Opin Neurobiol. 2007, 17 (5): 587-592. 10.1016\/j.conb.2007.11.003.","journal-title":"Curr Opin Neurobiol"},{"issue":"47","key":"716_CR36","doi-asserted-by":"publisher","first-page":"13419","DOI":"10.1021\/jp074285e","volume":"111","author":"ML Radhakrishnan","year":"2007","unstructured":"Radhakrishnan ML, Tidor B: Specificity in molecular design: a physical framework for probing the determinants of binding specificity and promiscuity in a biological environment. J Phys Chem B. 2007, 111 (47): 13419-13435. 10.1021\/jp074285e.","journal-title":"J Phys Chem B"},{"issue":"38","key":"716_CR37","doi-asserted-by":"publisher","first-page":"14952","DOI":"10.1073\/pnas.0702766104","volume":"104","author":"EJ Deeds","year":"2007","unstructured":"Deeds EJ, Ashenberg O, Gerardin J, Shakhnovich EI: Robust protein protein interactions in crowded cellular environments. Proc Natl Acad Sci USA. 2007, 104 (38): 14952-14957. 10.1073\/pnas.0702766104.","journal-title":"Proc Natl Acad Sci USA"},{"issue":"6","key":"716_CR38","doi-asserted-by":"publisher","first-page":"874","DOI":"10.1002\/cmdc.200700036","volume":"2","author":"K Azzaoui","year":"2007","unstructured":"Azzaoui K, Hamon J, Faller B, Whitebread S, Jacoby E, Bender A, Jenkins JL, Urban L: Modeling promiscuity based on in vitro safety pharmacology profiling data. ChemMedChem. 2007, 2 (6): 874-880. 10.1002\/cmdc.200700036.","journal-title":"ChemMedChem"},{"issue":"6","key":"716_CR39","doi-asserted-by":"publisher","first-page":"2445","DOI":"10.1021\/ci600197y","volume":"46","author":"A Bender","year":"2006","unstructured":"Bender A, Jenkins JL, Glick M, Deng Z, Nettles JH, Davies JW: \"Bayes affinity fingerprints\" improve retrieval rates in virtual screening and define orthogonal bioactivity space: when are multitarget drugs a feasible concept?. J Chem Inf Model. 2006, 46 (6): 2445-2456. 10.1021\/ci600197y.","journal-title":"J Chem Inf Model"}],"container-title":["BMC Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/1471-2210-10-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/1471-2210-10-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/1471-2210-10-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,1,22]],"date-time":"2019-01-22T06:10:57Z","timestamp":1548137457000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1186\/1471-2210-10-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,3,2]]},"references-count":39,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2010,12]]}},"alternative-id":["716"],"URL":"https:\/\/doi.org\/10.1186\/1471-2210-10-3","relation":{},"ISSN":["1471-2210"],"issn-type":[{"value":"1471-2210","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,3,2]]},"article-number":"3"}}