sign in sign up
<<
Home , Cromakalim, Diazoxide, Huwentoxin, Picrotoxin, Ralfinamide

467

Index a – 357 ff. a interaction domain 71 – 357 a1 subunit 69 ff. antiepileptic , sites 9 a2-d subunit 57, 69 ff. antiepileptics 87 a- (DTX) 217 anxiety 369 – selectivity 219 – canopy test 369 ff. A-278637 344 ff. apamin 242, 244, 326 f. A- 411873 323 apoptosis 237 acetylcholine receptor deficiency 408 –Fas receptor 237 AChR 410 – mitochondria 237 action potential 44, 55 aryloxindole 321 adipocytes 244 ff. arylpyrrole 323 – brown fat 244 asthma 324

– glucose transporter 244 ATP-sensitive KATP 335, – white fat 244 385 afterhyperpolarization 314 atrial effective refractory period (AERP) Agenelopsis aperta 131 291 alkaloid 319, 328 atrial fibrillation 276 ALMOND modul 432 ff. atrial vulnerability 291 Alzheimer’s disease 317 autism 396 ambasilide 278 autoantibodies 238 -sensitive epithelial sodium autoimmune diseases 247 ff. channel 397 autosomal dominant 4-aminopyridine 222 – juvenile myoclonic epilepsy 412 29, 278 – nocturnal frontal lobe epilepsy 410 , NaV blocking activity 186 auxiliary subunit in 89 ff. –Kvb 11 amygdala-kindling model 357 ff., 361 – KChIp1-4 11 91 – minK 11 ancillary subunits 69 ff., auxiliary subunits

77 –Cava210 Andersen-Tawil syndrome 383 –Cavb 10 anesthetics 87 –Cavd 10 anosmia 251 –Cavg 10 antiarrhythmic drugs 9, 278 –Navb19 –ofK+ channels 198 – amygdala-kindling 357 ff. AVE0118 287, 289 –6Hz model 361 azaindole 323 – maximal electroshock 357 ff. 278

Voltage-Gated Ion Channels as Targets. Edited by D. Triggle Copyright c 2006 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim ISBN 3-527-31258-7 468 Index

b – dialkyl-dipeptidylamines 132 b cell rest 341 – dihydropyridines 139 ff. b subunits 69 – ethanol 140 ff. b-cell overwork 341 – -I 127 b-tryptase inhibitors 440 – imidazolines 139 ff. b1-integrin 236 – non-specific N 128 B cell 215, 234, 237, 247 – 136 ff. – memory B cell 237 ff. – small organic molecule 132 ff. – proliferation 237 – substituted L-amino acids 132

–TCM 247 ff. – substituted piperidines 136 ff. –TEM 247 ff. – unsaturated hydrocarbons 138 ff. Ba2+ 86 – of the 128 Ball, channel expression 238 – volatile anaesthetics 139 89 ff. BMS 191011 322 Bartter syndrome 406 BMS-180448 338 – type 2 383 BMS-189269 320 – type 4 407 BMS-191095 338 barttin 406 BMS-204352 312, 321 Becker’s syndrome 403 Boltzmann curve 23 89 ff. Boltzmann function 26 benign familial neonatal bone resorption 250 – convulsions 388 borderline SMEI 395 – infantile seizures 396 Brugada syndrome 394 f. benzamides 235 29, 171 – binding site 227 – structure 172 –Hill coefficient 227 –PAC 227 c – SAR 227 CACNA1A 401 f. – selectivity 227 CACNA1C 400 – trans-N-propyl-carbamoyloxy PAC 227 CACNA1F 401 benzimidazolinone 326, 329 CACNA1H 403 benzimidazolone 320 CACNA1S 399 benzooxazolone 326, 329 CACNB4 402 benzothiazepine class 103 calcium activators 100 278 calcium channel 9, 65, 382, 399 binding 56 – L-type 27 biophysical properties 159 – N-type 122 – activation 160 –T-type 23, 27, 42, 84 – recovery from inactivation 160 calcium channel blockers 100 – state-dependent – abscisic acid 108 blocker 161 – amlodipine 102 – steady-state inactivation 160 – benzacocine CGP 108 – use-dependent 162 – benzothiazepine 103 bladder 245 – BMY 20064 104 – hyperactivity 315 – 115 –K+ channel expression 245 – calcludine 115 – overactivity 323, 326 – clotrimazole 114 blockers – 1,4-dihydropyridine 103 – aliphatic monoamines 138 ff. – 101 ff. – v-agatoxin-IIIA 128 – dodecanol 114 – conclusions 140 ff. – dodecylamine 114 – v--GVIA 127 – 102 – v-conotoxin MVIIC 128 – FPL 64176 108 Index 469

– gene delivery 118 –TEM 247 – HOE 166 104 CD4+ 233 – 102 CD8+ 233 –L652,469 104 CD27 234, 237 – L-calchin 115 CD45RA 233 f.

– MCI 176 104 –TEM 247 – McN-5691 104 CDP-840 434, 436

– McN-6186 104 central memory (TCM) 232 – MDL 12,330 104 cerebellar ataxia 314 – 104, 114 cetiedil 324 – 115 CFTR 407 – 102 CGS-7181 323 – 101, 103 CGS-7184 323 – 102 chalcone-16 230 – 115 – pharmacological properties 225 – phenylalkylamine 103 – selectivity 220 – praziquantel 117 channelopathy 381 ff., 412 – (–) S bay k 8644 108 (ChTX) 57, 216 f., 318 – (+) S 202-791 108 – selectivity 219 –SR33557 104 – sequence 218 – structure–activity relationships 102 childhood absence epilepsy 396 – tetrandine 104 chloride channel 382, 403 – tinuvin 770 114 chloroquine 430 – 101, 103 326 – vitamin D 115 CHO cells 429 –WAY 141520 117 chromanol 293B 278 calcium channel knockout 76 chronic constriction injury model 357 calcium currents chronic graft versus host disease (GvHD) – L-type 10, 65, 101 215, 237, 247 – N-type 10, 65, 123 – pathogenesis 250 –P/Q-type 10, 65 – therapies 250 – R-type 10, 65 ChTX 233, 235, 242, 245 f. –T-type 10, 65, 84 430, 434 calcium ions 65 ClCa 50 calcium signaling 235 ClC-1 403 calcium-activated K+ channel 196, 199 ff., 310 ClC-2 404 calcium-dependent inactivation 70 ClC-5 405 candidate gene approach 381 CLC-7 406 f. canopy test 369 ClC-Ka and ClC-Kb channels 406 f. 21, 32 CLCN-K 406 – derivatives 173 CLCN1 403 – metabolism 173 CLCN2 404 – neuropathic 173 CLCN5 405 – structure 173 CLCN7 406 carrageenan model 359 Clofilium 278 Cav1.1 399 ClogP 431 Cav1.2 400 clotrimazole 242, 319, 324 – L-type 31 CMR 431 Cav1.4 401 CNG Channels 390 f. Cav2.1 401 CoMFA 434 Cav2.2 32, 403 CoMSiA 434 CC2-DMPE 52 cone snail toxins CCR7 233 f., 250 – disulfide pattern 221 470 Index

– four disulfide bonds 221 – cardioprotective effects 338 congenital myasthenic syndromes 408 – b cell function 341 congenital stationary night blindness – 336 type 2 401 – 340 Conus catus 127 – nesidioblastosis 340 Conus geographus 130 – pharmacological tools 335 Conus magus 130 – polycystic ovary syndrome 340 – v-conotoxin-MVIIA 126 – side effects 341 conus striatus 130 DiBAC 51 f. v-conotoxin GVIA 66, 126 f. dichlorophenylpyrazolopyrimidines 228 v-conotoxin MVIIA 68 375 ff. CoroNa Green 58 dihydropyridine 21, 325 correolide 215, 217, 224, 235, 245 1,4-dihydropyrimidine 109 – C18-analog 227 1,4-dihydropyridine class 103 – binding-site 226 – activators 113 – pharmacological properties 225 – amlodipine 106, 108 – selectivity 220, 227 – benidipine 106 – spachea correa 226 – clinically available 110 – structure 223 – clinidipine 106 –Tcell proliferation 227 – conformational requirements 109 CP-339818 224 f. – felodipine 106 – selectivity 220, 225 – isradipine 106 – structure 223 – 106 CRAC 234, 236 – 106 crobenetine – 106 – properties 177 – nicardipine 106 – regiochemistry 176 – nifedipine 106 – structure 177 – 106 – treatment of ischemic stroke 177 – nimodipine 106 – 106 – bladder inhibitory effects 344 – 106 – cardioprotective effects 338 – NO-releasing activities 113 – clinical effects on bladder 343 – privileged structure 106, 114 –invitro (pig bladder strip) 347 – QSAR 109 – pharmacological tools 335 – state-dependence 110 cyclic nucleotide-gated channel 390 – state-dependent interactions 111 f. CYP2C9 inhibition 440 – stereoselectivity 107 cystic fibrosis 316, 407 – structure–activity relationships 107, 110 – vascular cardiac selectivity 111

d dihydropyridine KATP blocker 345 DC-EBIO 326 dihydropyridine KATP openers 345 de novo design 299 dihydropyridines 66, 89, 139 dehydrosoyasaponin-1 324 dihydroquinolones delayed type hypersensitivity (DTH) 236 – CP-339818 224 deltamethrin 55 – 125I-ChTX-displacement 224 dendrotoxin 57 – mechanism of channel block 224 Dent’s disease 405 – patch-clamp 224 DHS-1 324 – 86Rb-efflux 224 Di-ANEPPS 51, 55 – WIN-17317-3 224 diabetes 340 diisopyramide 28 dialkyl-dipeptidylamines 132 ff. diltiazem 21, 223, 278 diphenylurea 320 – antihypertensive 336 disease association 162 Index 471

– channelopathies 162 Filistata hibernalis 128, 131 – febrile seizures plus (GEFS+) type 2 163 28, 278 – GEFS+ type I 163 FLIPR 58 – hyperkalemic periodic paralysis 162 FLIPRr 33 – long Q-T syndrome type 3 163 88 ff. – myotonias 162 fluorescence 56 f. – paramyotonia congenita 163 fluorescence resonance energy transfer 429 – potassium aggravated myotonia 163 (Katadolonr) 355 ff. – primary erythermalgia 163 formalin model 359 ff. disease indications 246 ff. frequency dependence 45 distribution of VGCCs 66 FRET 52 f., 55 57 dopamine 328 g drain plug model 434 Gbg 74 278 GABAA 412 drug acquired LQTS 447 – receptors 412 drug binding sites 207 57 d- 278 gain of function 382 ff., 385, 388, 390 f., ducky mouse 77 393 ff., 403, 410 gate 22 e gating 208 EAE 247 – state 19 1-EBIO 317, 326, 329 gene 214 effector memory (TEM) 232 generalized febrile epilepsy plus 395, 397 89 ff. genetic and acquired channelopathies 381 electrical signals 7 GIRK 50 ENaC 397 GLRA 410 ENaC channel 397 GLRB 410 28 glucose transporter 244 epilepsy 77, 355 ff. glyburide epilepsy with grand mal seizures – anti-arrhythmic activity 339 on awakening 404 – antidiabetic agent 336 episodic ataxia 76 – -releasing properties 340 – type 1 386 – pharmacological tools 335 – type 2 401 receptors 410 epithelia 245 goats model of AF 291 –K+ channel expression 245 Grammostola spatulata 128, 130 epitope spreading 252 Grave’s disease 238 erectile dysfunction 322 green fluorescent protein 53 erg-2 242 GRIND-based model 432 57 [14C]-guanidium, ion flux 58 ethanol 140 g subunits 69 87 ff. 1-ethyl-2-benzimidazolinone 317 h 88 ff. f Hashimoto’s thyroiditis 238 familial hemiplegic migraine 401 HCN Channels 391 Fas receptor 237 hearing 314 – apoptosis 237 heart 246 fast channel syndrome 410 –K+ channel expression 246 febrile seizures associated with HEK cells 429 afebrile seizures 396 hERG 38, 55, 57, 59, 242, 389 f. felodipine 89 – channel 207, 428 472 Index

– channel mutations 430 IgD 234, 237

h-erg potassium channel 389, 444 ff. IKAch 50 – antihistamines 449, 454 IKR 42 – antipsychotic drugs 450 IKS 42 – arsenic trioxide 454 IKur 276 – 449 IL2 production 225 – blockers, not LQT 454 imidazolines 139 – cisapride 450 immunological 235 ff. – clarythromycin 453 imodipine 89 – clomiphene 454 inactivation 22 – erythromycin 453 incontinence 323 – fluoroquinolone antibacterials 450 indications 186 – grepafloxacin 450 indole urea 323 – haloperidol 450 infantile malignant osteopetrosis 406 – interactions 449 infantile spasms 395 – macrolide antibiotics 453 inflammatory pain 359 – sparfloxacin 450 inherited disorders 381 ff. – 450 insomnia 412 – trafficking effects 454 integrated risk assessment 444 ff., 455 ff. – verapamil 454 intermediate-conductance 310 high-throughput screening 33 intractable childhood epilepsy 395 high voltage activated (HVA) currents 66 inward rectifiers 200 ff., 383 hinge 14 inward-rectifying K+ channels 12, 196 HIV-related neuropathy 243 ion flux 57 f. HMR-1556 278 ischemia 320 HMR1883 340 ischemic preconditioning 337 Hodgkin–Huxley 20 IsK 386 – model 30 87 ff. homology model 300 isolated cardiac conduction defect 394 f. homopiperidine 324 isridapine 89 HQSAR, hologram QSAR 431 hyperekplexia 411 j hyperinsulinaemic hypoglycaemia Jervell and Lange-Nielson syndrome 387 of infancy 385 juvenile absence epilepsy 404 hyperinsulinemia 340 f. juvenile myoclonic epilepsy 402, 404 hyperkalaemic periodic paralysis 76, 393, 399 hyperpolarization-activated cyclic k

nucleotide gated channels 391 KATP drug-related patent applications 349 hypomagnesaemia with secondary KATP openers for alopecia 348 hypocalcaemia 392 KATP partial agonist 346 hypoxia 237 KATP radioligand 345 6Hz “psychomotor” test 361 kaliotoxin 215 ff., 246, 250 – selectivity 219 i – sequence 218 r IKr 389 Katadolon 355 iberiotoxin 319 KCa1.1 312, 318 ICA-17043 324 KCa2.1 327 ICH 444 ff. KCa2.2 327 – E14 446 KCa2.3 327 – guidelines 445 ff. KCa3.1 231, 238, 245 f., 315, 324 – S7A 446 ff. – expression 233 ff., 234

– S7B 446 KVb2 235 Ig-fold 9 K+ channel 11, 382, 385 Index 473

– auxiliary subunits 201 – null mice 215 – blockers 214 – olfactory bulb 214 – classification 194 – oligodendrocytes 214 – crystal structure 201 – osteoclasts 214 – diseases 194 – peptide inhibitors 216 – 29 – phosphorylation 235 – toxins 210 – physiological role 231 ff. KCMA3 312 – platelets 214 KCNA1 386 – single-channel conductance 231 KCNE1 386 f. Kv1.4 243 KCNE2 389 Kv1.5 240, 242 f. KCNH2 389 – 275 KCNJ1 383 – homology modul 275 KCNJ2 383 – pharmacophore model 275 KCNJ11 385 Kv1.6 232, 243 KCNMA1 312 Kv3.1 232 KCNMB1 314 – null mice 232 KCNN1 316 Kv7.2–7.5 355 KCNN2 316 Kv11.1 242 KCNN3 316 Kv11.2 242 KCNN4 315 Kvap channel 428 KCNQ channels 355 ff. KvLQT1 386, 388 KCNQ1 386 f. KYS05044 91 ff. KCNQ2 388 KCNQ3 388 l KCNQ4 388 Lambert-Eaton myasthenic syndrome 402 KCNT2 312 32, 175 ff. KcsA channel 428, 430 – binding site 170 ff. KDR kinase inhibitors 437 – history 168 khellinones 223 – indications 168 – chalcone-16 223, 227, 230 – 171 ff. –Hill coefficients 230 – sodium channel block 171 ff. – dimers 230 – structure 170 ff. – selectivity 230 large-conductance 310 kinetics 45 328 Kir1.1 383 lead identification 296 Kir2.1 241, 243, 383 – pharmacophore-based 299 Kir3 50 – structure-based 299 Kir4.1 243 lethargic mouse 77 Kir6.2 385 levosimendan 339, 349 KirBac1.1 channel 428 Liddle’s syndrome 397 Kv1.1 232, 385 f. 27 ff., 31, 175 ff., 181 ff. Kv1.2 232 – binding site 171 f. Kv1.3 – history 168 – apoptosis 237 – indications 168 – B-lymphocytes 214 – mechanism of block 169 ff. – expression 233 ff. – 168, 172 ff. – gene 214 – postherpetic neuralgia 172 ff. – hypoxia 237 – structure 172 – knockout mice 251 ligand binding 204

–KVb2 235 ligand operated channels 382 – macrophage 214 ligand-based – microglia 214 – chemometric models 430 474 Index

– model 428 memory T cells

ligand-gated channels 408 – central memory (TCM) 232 local anesthetics, receptor sites 9 – effector memory (TEM) 232 long QT syndrome (LQTS) 389 f., 444 methsuximide 87 ff. – type 1 386 5-methoxypsoralen 229 loss of function 382 ff., 383, 386 ff., 394 ff., 171, 175 ff. 401, 403, 405 f. – analogues 180 ff. low voltage acitvated (LVA) currents 65 – structure 172 L-type 66 mexilitine 21, 29 L-type calcium channel 42, 399 mibefradil 21, 24 f., 90 ff. – blockers 89 mice lacking the Kv1.3 232 – calcium activators 100 microglia 241 ff. – calcium antagonists 100 – ameboid 241 ff. – calcium channel blockers 100 –K+ channel 241 ff. – calcium entry blockers 100 – migration 242 – gabapentin 116 – proliferation 242 – 116 – ramified 241 ff. – splice variants 112 – respiratory burst 242 – state-dependent interactions 112 migraine 364 ff.

– a1-b subunit site of interaction 117 MinK 386 f. – a2d subunit 116 338, 348 L-type channel 100, 122 MiRP1 38, 389 f.

– 101 mitochondrial KATP (mito-KATP) channel 335, – flunarizine 101 337 – 100 – opener 338 – verapamil 100 MK-499 430, 434 LQT7 384 5-MOP, Structure 223 lymphocytes 55 modulated receptor hypothesis 46 modulated receptor model 24, 27 m monophasic action potentials (MAP) 291 macrophage 239 ff. MS 232, 237 f., 247 –KCa1.1 240 Mthk channel 428, 430 –K+ channel 239 multiple sclerosis (MS) 215 – Kir2.1 241 – EAE 247 –Kv1.3 239 –MSlesion 247 –Kv1.5 240 – myelin antigen-specific T cells 247 – membrane potential 240 – therapies 248 –[3H]thymidine incorporation 240 muscle acetylcholine receptors (AChR) 408 malignant hyperthermia 399 mutations 381 ff. 215 ff., 219, 232, 235, myasthenic syndrome 393 f. 237, 240, 245 myocardial ischemia 337 – pharmacological properties 225 myogenic bladder overactivity 343 – selectivity 219 myotonia congenita 403 – sequence 218

marketed KATP modulating drugs 336 n maxikdiol 324 NaV subtypes 169 maximal electroshock 357 NaV blockers 187 MaxiPostTM 321, 362 ff. – indications 186 M currents 355, 388 – neurodegenerative disease states 186 mechanisms of drug block 169 – new structural classes 180 – use-dependent 170 Na+-K+-ATPase 245 375 ff. natural killer cells 239 membrane potential sensing dyes 51 ff. Nav1.1 395 Index 475

Nav1.2 396 – v-conotoxin-GVIA 126

Nav1.4 393 – GABAB 123 Nav1.5 394 – inorganic cations 124 neurogenic bladder overactivity 343 – peptide blockers 125 neuroleptics 88 – specific blockers 125 neurological disorders 329 neuromuscular transmission 403 o neuronal AChR 410 obesity 251 neuropathic pain 355 ff. octanol 87 neuropeptide Y, Y5-receptor antagonists Ohm’s law 39 436 olfactory bulb 244 neuroprotection 322, 326 – super-smeller 244 NFAT 236 oligodendrocytes 243 ff. Ni2+ 86 – differentiation 243 nifedipine 27, 89, 325 –K+ expression 243 – structure 223 – precursors 243 night blindness 76 – proliferation 243 nimodipine 89 oocytes 429 NIP-141 284 Ornithoctonus huwena 131 NIP-142 284 – huwentoxin-I 127 nitrendipine 27, 89, 223, 325 OSK1 219 88 osteoclasts 245 ff. NMDA receptor 27 – bone resorption 246 NN414 341 f. –K+ channel expression 245 ff. NNC 55-0118 341 – membrane potential 246 NO-releasing activities, overactive bladder (OAB) 343 1,4-dihydropyridines 113 oxadiazolone 322 nociception 32, 320 non-selective cation channels 382, 390 p novel KATP chemotypes 347 PAC 224 NS-4 320, 322 –Hill coefficient 227 NS-8 323 – pharmacological properties 225 NS-309 326, 328 – selectivity 220, 227 NS-1608 320 – structure 223 NS-1619 320 – trans-N-propyl-carbamoyloxy PAC 227 NS-4591 328 pain 32, 76 NS-1619 314 pain (inflammatory), N-type 66 carrageenan assay 358 ff. N-type calcium channel pain (neuropathic) – blockers 123 ff. – chronic constriction injury (CCI) 357 ff. – pharmacology 123 – spared nerve assay 359 ff. N-type channel peptide antagonists – spinal nerve ligation 359 ff. – v-agatoxin IVA 131 – streptozoticin assay 369 ff. – v- 130 pain (persistent), formalin assay 358 ff.

– DW13.3 131 pancreatic b-cell KATP 335 – huwentoxin-I 131 PAP-1 217 – in vitro 130 – oral availability 229 – in vivo 130 – pharmacological properties 225 – kurtoxin 131 – selectivity 220, 229 – v-phonetoxin IIA 131 – structure 223 – SNX-325 131 Parabuthus transvaalicus 131 N-type channels 403 Paramyotonia congenita 393 –Cav2.2 122 f. patch clamp 39 ff., 59 476 Index

– assay 429 platelets 246 240, 319 –K+ channel expression 246 Pb2+ 86 polymerase chain reaction 381 PBFI 58 pore 9-10, 12 f. PDE4 inhibitors 434 Posicorä 90 penfluridol 88 ff. positional cloning 381 pentylenetetrazol 357 ff. potassium channels; see K+ channel 11, 382, peptide inhibitors 216 ff. 385 peptide toxins 318, 327 potassium selctivity region 428 peptidomimetic 228 potassium-aggravated myotonia 393 Per-Arnt-Sim domain 428 P/Q-type 66 pharmacophore model 299 pregabalin 57 –3-dimensional 431 Prialtr () 32 87 ff. primary and tertiary structure 152 phenyl-stilbene A 228 – IFM motif 154 – structure 223 – membrane topology 152 phenylalkylamine class 105 – P-loop 152 20, 27, 32, 87 ff., 175 ff. privileged structures 103, 296 – history 168 230 – indications 168 278 – neurodegenerative disease states 186 87 ff. – neuroprotection 174 ff. prostate cancer 326 – structure 174 ff. protein crystal structure 59 phoneutria nigriventer 131 protein kinase C 73 – venom of the spiders 128 protein superfamily 7 phylogenetic analysis 154 ff. provisional safety margins, – evolutionary perspective 156 ff. 30-fold margin 456 – four-domain family 154 ff. pseudohypoaldosteronism type 1 397 –Nachannel genes 156 ff. psora-4 217, 224, 235 – SCN1A 157 ff. –Hill coefficient 229 – SCN2A 157 ff. –PAP-1 229 – SCN3A 157 ff. – pharmacological properties 225 – SCN4A 157 ff. – selectivity 220, 229 – SCN5A 157 ff. – structure 223 – SCN8A 157 ff. psoralens 224 – SCN9A 157 ff. – H37 229 – SCN10A 157 ff. –5-methoxypsoralen 229 – SCN12A 157 ff. –PAP-1 229 physicochemical models, 2-dimensional 431 – pharmacophore 229 pig model of AF 291 – psora-4 229 335 f., 341, 347 – ruta graveolens 229 – cardioprotective effects 338 – SARs 229 88 ff. psoriasis 215, 247 piperidines – autoantigens 249 – binding site 226 – pathogenesis 249 –Hill coefficient 226 – therapies 250 – patch clamp 226 purkinje fiber 59 – 86Rb-efflux 226 – selectivity 226 q – UK-78282 226 QT interval 384 f., 387 f., 390, 394 f.

pKa 431 QT-prolongion 434 PKA kinase anchoring proteins 73 quantitative structure activity relationship planar patch clamp 48 ff. (QSAR) 431 Index 477 28, 278 – sequence 218 quinine 223 – structure 216 quinolinium 328 screen sequence 38 quinolinone 322 SCREENIT 457 sea anemone toxins 221 r – disulfide pattern 221 RA 247 – functional dyad 221 177 ff. – sequence 218, 221 – pain models 178 ff. – structure 221 – 178 ff. seal resistance 48 – SAR (structure–activity relationship) Segestria florentina 128, 131 nd 178 ff. selective 2 generation KATP modulating – structure 177 drugs 349 f. – treatment of neuropathic pain 177 ff. selectivity 86Rb, ion flux 58 – herg channel 301 reduced repolarization reserve 457 –Kv1.5 301 remodeled atria 291 440 rescaffolding 298 severe myoclonic epilepsy of infancy 395 restenosis 316 ShK 215, 248 355 ff. – pharmacological properties 225 retina 245 – selectivity 220, 222 –K+ channel expression 245 – ShK-Dap 220, 222, 235 retinitis pigmentosa 390 – ShK-F6CA 220, 222 rheumatoid arthritis (RA) 215, 237 – structure 221 – pathogenesis 249 ShK(L5) 217, 220, 222, 225, 235 f., 246 – synovial fluid 249 – plasma level 248 right bundle branch block 395 – selectivity 222 326, 329 – toxicity 248 R-type 66 sickle cell anemia 324 rubidium efflux assay 428 f. similarity searches 298 Ruta graveolens 229 sinus node dysfunction 391 ryanodine receptor 399 site-directed mutagenesis 50, 302 Sjgren’s syndrome 238 s SKCa 327 S20951 289 Slo 312 safety pharmacology 444 slow channel syndrome 409 small molecules inhibitors 222 – epilepsy 177 ff. small-conductance 310

–Parkinson’s disease 177 ff. smooth muscle KATP 335 – restless legs syndrome 177 ff. snake toxins – structure 177 – a-dendrotoxin 220 SAR 137 f. – disulfide pattern 220 sarcolemmal cardiac KATP 335 SNX-482 68 – blocker 339 sodium channel expression 157 SBFI 58 – central nervous system 157 SCN1A 395 – peripheral nervous system 157 SCN2A 396 – subcellular expression 158 SCN4A 393 sodium channels 7, 28, 31, 151, 382, 397 SCN5A 394 f. spinal nerve ligation (SNL) SCNB1 397 (Chung) model 361 ff. toxins spinocerebellar ataxia 76 – contacts with channel 216 – type 6 401 – disulfids pattern 216 S4 regions 30 f. 478 Index

S4 segment 30 TEM 236 ff., 247, 247 ff. SS9947 289 terfenadine 430, 434 SSR149744C 278 207, 222 stargazer 77 tetraphenylporphyrins 228 state-dependent 56, 112 – structure 223 – block 44, 112 (TTX) 42, 168 – inhibition 20, 112 – in vivo evaluation 178 ff. states 37 ff., 46 ff., 53, 112 – structure 178 ff. – closed 37, 44 ff., 55, 112 TH-1177 91 ff. – inactivated 37, 44, 46, 55, 112 thermal hyperalgesia 359 – open 37, 44 f., 55, 112 Thomsen’s disease 403 steroids 230 thorough QT/QTc study 448 Stichodactyla helianthus (ShK) three-dimensional QSAR 434 – ShK(L5) 217 torsade de pointes 449 – ShK-Dap22 217 toxins 86 – ShK-F6CA 217 TRAM-34 232, 236, 240, 248, 315 streptozotocin model 369 TRAM-39 324 stroke 243, 322 transient receptor potential channels 392 structure-based model 428 transmural dispersion of repolarization 458 subdural hematoma 325 transplant rejection substituted L-amino acids 132 ff. – pathogenesis 250 sulfimidebenzamidoindanes 228 – therapies 250 -receptor 208, 385 triphenylmethyl 324 super-smeller 244 triterpene 324 SUR1/Kir6.2 openers 340 TRPM6 392 SUR2B splice variants 344 TTX SUR2B/Kir6.2 openers 343 – analgesia 180 ff. surface plasmon resonance 429 – binding site 169 ff. synprint 75 – blocking properties 169 ff. syntaxin 1 75 – in vivo efficacy 179 ff. systemic lupus erythematosus 238 – neurodegenerative disease states 186 – selectivity 169 ff. t two-electrode voltage clamp 50 tactile 359 ff. two-pore K+ channels 197, 200 ff. tail current 44 3H-thymidine incorporation 225 T cell 215, 231 ff. T-type 66 – 3H-thymidine incorporation 225 T-type Ca2+ channels 42, 84 – activation 234 – CACNA1G 84 – calcium signaling 235 – CACNA1H 84 – human 231 ff. – CACNA1I 84 – IL2 production 225 –Cav3.1 (or a1G) 84 – membrane potential 235 –Cav3.3 (a1I) 84 – memory 232, 250 – characteristics 85 – minipig 231 ff. – 92 – mouse 231 ff. – function 93 – na 231 ff., 250 – knockout mice 93 – proliferation 225, 233 – methodology 85 – rat 231 ff. – nociception 94

–TCM 236 ff. – pharmacology 86 –TEM 236 ff. – splice variants 85 tlymphocyte 231 ff. – thalamic dysrhythmias 94

TCM 236 ff., 247 ff. T-type channels 403 T1DM 247 type-1 diabetes mellitus (T1DM) 215, 237 Index 479

– GAD65 249 – block 27, 54 – insulin 249 – inhibition 20 – pathogenesis 249 voltage-gated calcium channels (VGCC) tyrosine kinase 235 – high voltage activated (HVA) 84 – low voltage activated (LVA) 84 u – subunit 85 U-92032 91 ff. voltage-gated K+ channels 194, 199 ff. UCL-1606 324 voltage-gated sodium channels 151, 393 UCL-1608 324 – action potential generation 151 UCL-1684 328 – blockers 168 UK-78282 – drugs 168 –Hill coefficient 226 – impulse propagation 151 – pharmacological properties 225 – membrane proteins 151 – selectivity 226 voltage-sensing UK78282 235 –S4segments 14 – selectivity 220 – dyes 43 – structure 223 urinary incontinence 316 w use dependence 28, 45 waggler 77 – inhibition 20 WAY-133537 344 WIN 17317-3 319 v WIN-17317-3 224 V=IR 53 – pharmacological properties 225

V0.5,inact 47 – structure 223 valproic acid 87 ff. vascular smooth muscle 55 x ventricular arrhythmia 339 XE-991 358 ff., 359 verapamil 90, 278 xenopus oocytes 39, 50 – stereoselectivity 105 – structure 223 y veratridine 55 Y5- 437 VGCC modulation 72 vinpocetine 174 z – structure 175 ZD0947 343 vitamin D 115 ZD6169 343 f. volatile anaesthetics 139 ZM244085 344 f., 347 volsurf 431 Zn2+ 86 voltage-dependent 87 ff.