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Appendix 1 Cross-Reference of Research, Generic and Trade Names of

Table 1. research designations with corresponding generic names

Research Designation Generic Name lactam methyloxazepam A 101 AB 35616 AB 39083 clorazepate AH 3232 clorazepate CB 4261 CB 4306 clorazepate CB 4311 clorazepate CGS 8216 (antagonist) CI683 CS 370 CS 430 D40TA EGYT 341 ER 115 temazepam HR 158 HR376 HR 4723 clobazam HR930 K3917 temazepam 287 THE BENZODIAZEPINES

Research Designation Generic Name

LA 111 LM 2717 clobazam ORF 8063 Ro 4-5360 Ro 5-0690 Ro 5-0883 desmethy1chlordiazepoxide Ro 5-2092 demoxepam Ro 5-2180 desmethyldiazepam Ro 5-2807 diazepam Ro 5-2925 desmethylmedazepam Ro 5-3059 nitrazepam Ro 5-3350 Ro 5-3438 Ro 5-4023 Ro 5-4200 Ro 5-4556 Ro 5-5345 temazepam Ro 5-6789 Ro 5-6901 Ro 15-1788 (antagonist) Ro 21-3981 RU 31158 loprazolam S 1530 SAH 1123 isoquinazepam SAH 47603 temazepam SB 5833 SCH 12041 SCH 16134 U 28774 U 31889 U 33030 W4020 We 352 triflubazam

288 RESEARCH, GENERIC AND TRADE NAMES

Research Designation Generic Name

We 941 Wy 2917 temazepam Wy 3467 diazepam Wy 3498 oxazepam Wy 3917 temazepam Wy 4036 Wy 4082 Wy 4426 oxazepam Y 6047 ciotiazepam

Table 2. Benzodiazepine generic names with corresponding trade names

Generic Name Trade Name(s) alprazolam Xanax bromazepam Compendium, Lectopam, Lexatin, Lexomil, Lexotan, Lexotanil brotizolam Lendorm, Lendormin camazepam Albego, Limpidon, Paxor chlordiazepoxide Ansiacal, A-Poxide, Benzodiapin, Binomil, Cebrum, Chlortran, Corax, C-Tran, Decacil, Diazepina, Disarim, Eden-psich, Endequil, Elenium, Equibral, Helogaphen, Huberplex, Klopoxid, Labican, Liberans, Librium, Libritabs, Lixin, Medilium, Menrium, Mesural, Multum, Nack, Normide, Novopoxide, O.CM., Omnalio, Philicorium, Psicofar, Psicoterina, Raysedan, , Relaxil, Reliberan, Risachief, Risolid, Seren, Silibrin, Sintesedan, Smail, Solium, SonimenTrilium, Tropium, Viansin, Zeisin, Zetran c10bazam Castilium, Frisin, Frisium, Karidium, Noiafren, Sentil, Urbadan, Urbanol, Urbanyl 289 THE BENZODIAZEPINES

Generic Name Trade Name(s)

clonazepam Clonopin, Iktorivil, Landsen, Rivotril clorazepate Azene, Belseren, Covengar, Enadine, Justum, Mendon, Moderane, Nansius, Tencilan, Transene, Tranxen, Tranxene, Tranxilen, Tranxilene, Tranxilium, Uni-Tranxene clorazolam see triazolam Rize, Trecalmo cloxazolam Enadel, Lubalix, OIcadil, Sepazon, Tolestan diazepam Aliseum, Alupram, Amiprol, Ansiolin, Apaurin, Apozepam, Armonil, Atenex, Atensine, Atilen, Avex, Best, Bialzepam, Calmpose, Ceregulart, Cuadel, Cyclopam, Diaceplex, Diapam, Diatran, Diazemuls, Dipam, Dipezona, Dizam, Doval, Drenian, D-Tran, Ducene, E-Pam, Eridan, Euphorin, Evacalm, Faustan, Gradual, Gubex, Lembrol, Levium, Lorinon, Meval, Morostan, Neo-Calme, Neurolytril, Noan, Notense, Novodipam, Pacitran, Pax, Paxate, Paxel, Plidan, Pro-pam, Quetinil, Quievita, Relanium, Relivan X, Saromet, Scriptopam, Sedapam, Sedaril, Seduxen, Serenack, Setonil, Solis, Somasedan, Sonacon, Stesolid, Stesolin, Stess-Pam, Tensium, Tranimul, Tranquase, Tranquirit, Tranquo-Tablinen, Valitran, Valium, Valrelease, Vatran, Vival, Vivol estazolam Domnamid, Esilgan, Eurodin, Nuctalon fiudiazepam Erispan fiunitrazepam Darkene, Narcozep, Primun, Rohipnol, Rohypnol, Roipnal, Val sera

290 RESEARCH, GENERIC AND TRADE NAMES

Generic Name Trade Name(s) flurazepam Benozil, Dalmane, Dalmadorm, Dalmate, Domodor, Dormodor, Felison, Felmane, Flunox, Fordrim, Insumin, Lunipax, Midorm AR, Natam, Niotal, Remdue, Somlan, Valdorm Coreminal halazepam Paxipam haloxazolam Some lin ketazolam Anxon, Contamex, Loftran, Solatran, Unakalm loprazolam Avlane, Dormonoet lorazepam Almazine, Aplaeasse, Ativan, Control, Emotieal, Emotival, Kalmalin, Loraus, Lorax, Lorsilan, Lorenin, NIC, Orfidal, Plaeidia, Psieopax, Quait, Seeurit, Sedarkey, Sedatival, Sidenar, Tavor, Temesta, Trapax, Wypax lormetazepam Loramet, Noetamid medazepam Ansilan, Anxitol, Azepamid, Benson, Diepin, Elbrus, Esmail, Lerisum, Medazepol, Megasedan, Metonas, Mezepan, Narsis, Navizil, Nivelton, Nobrium, Pazital, Psiquium, Raporan, Resmit, Rudotel, Serenium, Siman, Templane, Tranquilax Melex midazolam Dormieum nimetazepam Elimin, Erimin, Hypnon

291 THE BENZODIAZEPINES

Generic Name Trade Name(s) nitrazepam Apodorm, Arem, Benzalin, Calsmin, Dormicum, Dumolid, Eatan, Eunoctin, Hipsal, Hypnotin, Mitidin, Mogadan, Mogadon, Nelbon, Neuchlonic, Nipam, Nitrados, Nitrenpax, Noctene, Pacisyn, Paxisyn, Pelson, Persopir, Prosonno, Quill, Radedorm, Relact, Remnos, Sindepres, Somnased, Somnibel, Somnite, Sonebon, Sonnolin, Surem, Unisomnia nordazepam Calmday, Demadar, Madar, Stilny oxazepam Adumbran, Aplakil, Benzotran, Enidrel, Isodin, Limbial, Murelax, Nesontil, Nulans, Oxadin, Oxepam, Praxiten, Psiquiwas, Purata, Quen, Quilibrex, Sedokin, Serax, Serenal, Serenid-D, Serenid Forte, Serepax, Seresta, Serpax, Sobile, Sobril, Wakazepam Convertal, Hializan, Serenal Tranquit oxazolazepam see oxazolam Domar, Duna prazepam Centrax, Demetrin, Equipaz, Lysanxia, Mono Demetrin, Prazene, Reapam, Sedapran, Trepidan, Verstran temazepam Cerepax, Euhypnos, Lenal, Levanxene, Levanxol, Mabertin, Maeva, Normison, Planum, Remestan, Restoril, Signopam tetrazepam Clinoxan, Musaril, Myolastan tofisopam Grandaxin, Grandaxine, Seriel tofizopam see tofisopam triazolam Halcion

292 RESEARCH, GENERIC AND TRADE NAMES

Table 3. Benzodiazepine trade names with corresponding generic names

Trade Name Generic Name

Adumbran oxazepam Albego camazepam Aliseum diazepam Almazine lorazepam Alupram diazepam Amiprol diazepam Ansiacal chlordiazepoxide Ansilan medazepam Ansiolin diazepam Anxitol medazepam Anxon ketazolam Apaurin diazepam Aplacasse lorazepam Aplakil oxazepam Apodorm nitrazepam A-Poxide chlordiazepoxide Apozepam diazepam Arem nitrazepam Armonil diazepam Atenex diazepam Atensine diazepam Atilen diazepam Ativan lorazepam Avex diazepam Avlane loprazolam Azene c!orazepate Azepamid medazepam Belseren c!orazepate Benozil flurazepam Benson medazepam Benzalin nitrazepam

293 THE BENZODIAZEPINES

Trade Name Generic Name

Benzodiapin chlordiazepoxide Benzotran oxazepam Best diazepam Bialzepam diazepam Binomil chlordiazepoxide Calmday nordazepam Calmpose diazepam Calsmin nitrazepam Castilium c!obazam Cebrum chlordiazepoxide Centrax prazepam Ceregulart diazepam Cerepax temazepam Chlortran chlordiazepoxide Clinoxan tetrazepam Clonopin c!onazepam Compendium bromazepam Contamex ketazolam Control lorazepam Convertal oxazolam Corax chlordiazepoxide Coreminal fiutazolam Covengar c!orazepate C-Tran chlordiazepoxide Cuadel diazepam Cyc!opam diazepam Dalmane fiurazepam Dalmadorm fiurazepam Dalmate fiurazepam Darkene fiunitrazepam Decacil chlordiazepoxide Demadar nordazepam Demetrin prazepam

294 RESEARCH, GENERIC AND TRADE NAMES

Trade Name Generic Name

Diaceplex diazepam Diapam diazepam Diatran diazepam Diazemuls diazepam Diazepina chlordiazepoxide Diepin medazepam Dipam diazepam Dipezona diazepam Disarim chlordiazepoxide Domar pinazepam Domnamid estazolam Domordor flurazepam Dormicum midazolam, nitrazepam Dormodor flurazepam Dormonoct loprazolam Doval diazepam Drenian diazepam D-Tran diazepam Ducene diazepam Dumolid nitrazepam Duna pinazepam Eatan nitrazepam Eden-psich chlordiazepoxide Edenquil chlordiazepoxide Elbrus medazepam Elenium chlordiazepoxide Elimin nimetazepam Emotical lorazepam Emotival lorazepam Enadel cloxazolam Enadine clorazepate Enidrel oxazepam E-Pam diazepam

295 THE BENZODIAZEPINES

Trade Name Generic Name

Equibral chlordiazepoxide Equipaz prazepam Eridan diazepam Erimin nimetazepam Erispan fludiazepam Esilgan estazolam Esmail medazepam Euhypnos temazepam Eunoctin nitrazepam Euphorin diazepam Eurodin estazolam Evacalm diazepam Faustan diazepam Feliston flurazepam Felmane flurazepam Flunox flurazepam Fordrim flurazepam Frisin c10bazam Frisium c10bazam Gradual diazepam Grandaxin tofisopam Grandaxine tofisopam Gubex diazepam Ha1cion triazolam Helogaphen chlordiazepoxide Hializan oxazolam Hipsal nitrazepam Huberplex chlordiazepoxide Hypnon nimetazepam Hypnotin nitrazepam Iktorivil c10nazepam Insumin flurazepam Isodin oxazepam

296 RESEARCH, GENERIC AND TRADE NAMES

Trade Name GenericName

Justum c10razepate Kalmalin lorazepam Karidium c10bazam Klopoxid chlordiazepoxide Labican chlordiazepoxide Landsen c10nazepam Lectopam bromazepam Lembrol diazepam Lenal temazepam Lendorm brotizolam Lendormin brotizolam Lerisum medazepam Levanxene temazepam Levanxol temazepam Levium diazepam Lexatin bromazepam Lexomil bromazepam Lexotan bromazepam Lexotanil bromazepam Liberans chlordiazepoxide Limbial oxazepam Librium chlordiazepoxide Libritabs chlordiazepoxide Limpidon camazepam Lixin chlordiazepoxide Loftran ketazolam Loramet lormetazepam Loraus lorazepam Lorax lorazepam Lorinon diazepam Lorsilan lorazepam Lorenin lorazepam Lubalix c1oxazolam

297 THE BENZODIAZEPINES

Trade Name GenericName

Lunipax flurazepam Lysanxia prazepam Mabertin temazepam Madar nordazepam Maeva temazepam Medazepol medazepam Medilium chlordiazepoxide Megasedan medazepam Melex mexazolam Mendon clorazepate Menrium chlordiazepoxide Mesural chlordiazepoxide Metonas medazepam Meval diazepam Mezepan medazepam Midorm AR flurazepam Mitidin nitrazepam Moderane clorazepate Mogadan nitrazepam Mogadon nitrazepam Mono Demetrin prazepam Morostan diazepam Multum chlordiazepoxide Murelax oxazepam Musaril tetrazepam Myolastan tetrazepam Nack chlordiazepoxide Nansius clorazepate Narcozep flunitrazepam Narsis medazepam Natam flurazepam Navizil medazepam Nelbon nitrazepam

298 RESEARCH, GENERIC AND TRADE NAMES

Trade Name Generic Name

Neo-Calme diazepam Nesontil oxazepam Neuchlonic nitrazepam Neurolytril diazepam NrC lorazepam Niotal flurazepam Nipam nitrazepam Nitrados nitrazepam Nitrenpax nitrazepam Nivelton medazepam Noan diazepam Nobrium medazepam Noctamid lormetazepam Noctene nitrazepam Noiafren clobazam Normide chlordiazepoxide Normison temazepam Notense diazepam Novodipam diazepam Novopoxide chlordiazepoxide Nuctalon estazolam Nulans oxazepam O.C.M. chlordiazepoxide Okadil cloxazolam Omnalio chlordiazepoxide Orfidal lorazepam Oxadin oxazepam Oxepam oxazepam Pacisyn nitrazepam Pacitran diazepam Pax diazepam Paxate diazepam Paxel diazepam

299 THE BENZODIAZEPINES

Trade Name Generic Name

Paxipam halazepam Paxisyn nitrazepam Paxor camazepam Pazital medazepam Pelson nitrazepam Persopir nitrazepam Philicorium chlordiazepoxide Placidia lorazepam Planum temazepam Plidan diazepam Praxiten oxazepam Prazene prazepam Primun flunitrazepam Pro-Pam diazepam Prosonno nitrazepam Psicofar chlordiazepoxide Psicopax lorazepam Psicoterina chlordiazepoxide Psiquium medazepam Psiquiwas oxazepam Purata oxazepam Quait lorazepam Quen oxazepam Quetinil diazepam Quievita diazepam Quilibrex oxazepam Quill nitrazepam Radedorm nitrazepam Raporan medazepam Raysedan chlordiazepoxide Reapam prazepam Reposal chlordiazepoxide Relact nitrazepam

300 RESEARCH, GENERIC AND TRADE NAMES

Trade Name Generic Name

Relanium diazepam Relaxil chlordiazepoxide Reliberan chlordiazepoxide Relivan X diazepam Remdue flurazepam Remestan temazepam Remnos nitrazepam Resmit medazepam Restoril temazepam Risachief chlordiazepoxide Risolid chlordiazepoxide Rivotril clonazepam Rize clotiazepam Rohipnol flunitrazepam Rohypnol flunitrazepam Roipnal flunitrazepam Rudotel medazepam Saromet diazepam Scriptopam diazepam Securit lorazepam Sedapam diazepam Sedapran prazepam Sedaril diazepam Sedarkey lorazepam Sedativil lorazepam Sedokin oxazepam Seduxen diazepam Sentil clobazam Sepazon cloxazolam Serax oxazepam Seren chlordiazepoxide Serenack diazepam Serenal oxazepam, oxazolam

301 THE BENZODIAZEPINES

Trade Name Generic Name

Serenid-D oxazepam Serenid Forte oxazepam Serenium medazepam Serepax oxazepam Seresta oxazepam Seriel tofisopam Serpax oxazepam Setonil diazepam Sidenar lorazepam Signopam temazepam Silibrin chlordiazepoxide Siman medazepam Sindepres nitrazepam Sintesedan chlordiazepoxide Smail chlordiazepoxide Sobile oxazepam Sobri! oxazepam Solatran ketazolam Solis diazepam Solium chlordiazepoxide Somasedan diazepam Some1in haloxazolam Somlan flurazepam Somnased nitrazepam Somnibel nitrazepam Somnite nitrazepam Sonacon diazepam Sonebon nitrazepam Sonimen chlordiazepoxide Sonnolin nitrazepam Stesolid diazepam Stesolin diazepam Stess-Pam diazepam

302 RESEARCH, GENERIC AND TRADE NAMES

Trade Name Generic Name

Stilny nordazepam Surem nitrazepam Tavor lorazepam Temesta lorazepam Templane medazepam Tencilan clorazepate Tensium diazepam Tolestan cloxazolam Tranimul diazepam Tranquase diazepam Tranquilax medazepam Tranquirit diazepam Tranquit oxazolam Tranquo-Tablinen diazepam Transene clorazepate Tranxen clorazepate Tranxene clorazepate Tranxilen clorazepate Tranxilene clorazepate Tranxilium clorazepate Trapax lorazepam Trecalmo clotiazepam Trepidan prazepam Trilium chlordiazepoxide Tropium chlordiazepoxide Unakalm ketazolam Unisomnia nitrazepam Uni-Tranxene clorazepate Urbadan clobazam Urbanol clobazam Urbanyl clobazam Valdorm flurazepam Valitran diazepam

303 THE BENZODIAZEPINES

Trade Name Generic Name

Valium diazepam Val release diazepam Val sera fiunitrazepam Vatran diazepam Verstran prazepam Viansin chlordiazepoxide Vival diazepam Vivol diazepam Wakazepam oxazepam Wypax lorazepam Xanax alprazolam Zeisin chlordiazepoxide Zetran chlordiazepoxide

304 Appendix 2: Books on Benzodiazepines

Costa E (ed): The Benzodiazepines: From Molecular Biology to Clinical Practice. New York, Raven Press, 1983.

CostaE, Di Chiari G, Gessa GL (eds): GABA and Benzodiazepine Receptors. New York, Raven Press, 1981.

Costa E, Greengard P (eds): Mechanisms of Action of Benzodiazepines. New York, Raven Press, 1975.

Garattini S, Mussini E, Randall LO (eds): The Benzodiazepines. New York, Raven Press, 1973.

Greenblatt DJ, Shader RI: Benzodiazepines in Clinical Practice. New York, Raven Press, 1974.

Marks, J: The Benzodiazepines: Use, Overuse, Misuse, . 2nd Edn. Lancaster, England, MTP Press Limited, 1985.

Priest RG, Vianna Filho U, Amrein R, et al. (eds): Benzodiazepines Today and Tomorrow. Lancaster, England, MTP Press Limited, 1980.

Skolnick P, Tallman JF, Jr., et al. (eds): Pharmacology of Benzodiazepines. London, The Macmillan Press, Ltd., Scientific and Medical Division, 1982.

Szara SI, Ludford JP: Benzodiazepines: A Review of Research Results, 1980. NIDA Research Monograph 33. Rockville, Maryland, National Institute on Abuse, 1981.

305 Index

absorption rates intravenous 46 factors affecting 49 oral 46-8 122, 124, 125, adaptation 52 oral benzodiazepines 46-8 see dependence, abuse and abuse 35,36 withdrawal behavioral effects 193,194 adverse drug reactions 2 see also tolerance, negative 193 , dependence and withdrawal benzodiazepine avoidance 95 10 benzodiazepines used 189, 190 behavioral 131 new 190 and benzodiazepine abuse 95 cortical atrophy 194 clobazam 154 definition 181 clonazepam 165 and dependence differences 194,195 eNS 99 diazepam, Third World 172 early morning 129-31 disorder classification 181 fiurazepam 139 experimental assessment 201-7 49 drug abuse 210-14 hypnotics 127-31 human self-administration 205,206 daytime sedation 127-9 human studies 209-23 129 comparison 215 initial treatment 53,60 placebo comparison 215 metabolism 102 forecasting potential 191-3 performance 10 animal studies 191 psychotropic 60 human volunters 191-3 sedation 93,117 international legislation 269-71 social 76 liability 202 temazepam 140 mUltiple 186,187 tricyclic 117 potential 2, 117 triazolam 131, 139 primary 103-6 tryptophan 161 international data 184 aggression secondary 179,186-90,194,195 enhancement 100,101 and 186 reduction 9 euphoriant 189 alcohol use and abuse narcotics and 187 112 reasons and narcotics 188, 189 benzodiazepine reinforcement 210,212, urine test 187 213 socio-medical appraisal 195 benzodiazepine social cost 282 street cost 188 cross-tolerance 93, 95 , drug incidence 186 psychotropic 76,77 activity onset 45-9,99 withdrawal 159-65 and use 124,125 alprazolam, half-life 97,98

307 BENZODIAZEPINES

American Psychiatric Association, abuse behavioral tests, 9 classification 181,182 behavioral toxicity 228-31 see also toxicity 'Y aminobutyric acid see also GABA benefit/cost aspects, drug controls 278,279 16 benefit/risk ratio 116 CNSroie 7 Benzodiazepine Research and Training inhibitory neurotransmission 14 Project 3 presynaptic inhibition 14 bicuculline 16 amnesia, anterograde 10 binding sites anesthesia 88, 165 CNS 21-4 diazepam in Third World 171, 172 and receptors 24 animal studies blood- barrier 45 abuse potential 191 brain regions and benzodiazepine effects 17 self-administration 205 brain stem, benzodiazepine effects 17 anti-anxiety drugs breast milk, drug exposure 228 overprescription III bromazepam abuse 190 sex bias and use 255,258 structures 88 caffeinism 80 synonyms 112 anxiety 115 activity 7, 8 tranquilo- use 80 neuronal activities 34 cancer risk and diazepam use 260,261 antiepileptic action 34 cerebellar cortex, benzodiazepine effects 17 anxiety 17 acute and chronic 113,114 !3-CCE, benzodiazepine antagonism 26,27 assessment 114 !3-CCM, benzodiazepine antagonist 26,27 benzodiazepinetherapy 253,254 !3-CCPr, benzodiazepine antagonism 26,27 benzodiazepine use III , onset of effects and causes 115 plasma invasion 60 and change 116 CGS 8216, receptor blocking 26 chronic treatment 59-64 chlordiazepoxide daytime 129,133 abuse 189,221 definitions 112, 113 alcohol withdrawal 160,161 non-psychotic 97 anxiolytic half-life 97,98 non-psychotropic treatment 112 discovery 1 physician response III eclamptic seizures 154 rebound 242 abuse comparison 218 treatment 116, 117 chloroquine toxicity !3-blockers 117, 118 incidence 170,171 guidelines 118, 119 mortality and diazepam 170, 171 tricyclic antidepressants 117 views of III alcohol withdrawal 160 anxiolytic effects diazepam interaction 56 benzodiazepines 97-105 and clearance 56 mechanism 34,35 clobazam non-sedative role 10 anticonvulsant use 153 area under the time-action curve 218 serum concentrations 5 I assessment clonazepam anxiety 114 anticonvulsant interaction 152 benzodiazepine uses 284 gradual onset 152 autonomic affects 10, 11 164 autoradiography, benzodiazepine binding status epilepticus 150, 15 I sites 21,22 clorazepate abuse 222 , benzodiazepine receptor half-life, anxiolytic 97,98 actions 30 seizure use 153 Beck Scale 115 231 behavioral effects cognitive impairment 229 anti punishment 9 commercial availability, international exploratory 9 comparison 69,70 behavioral inhibition system 35 conjugation, factors affecting 55,56 308 INDEX controls anxiolytic half-life 97,98 international 268,269 biotransformations 55 local, psychotropics 267,268 and cancer 260,261 convulsions, electroshock-induced 8 chlordiazepoxide abuse comparison 221 cross-dependence 202 abuse comparison 215, cross-tolerance 93,95 216 crutch phenomena 79, 183 clorazepate abuse comparison 222 conditions prescribed 254 daytime sedation 127-9 eclamptic seizures 154 defined daily dose 71-3 halazepam abuse comparison 221 dependence 11, 12 see a/so withdrawal initial response and outcome 102 and 179, 241 life saving 165 animal studies 203 lorazepam abuse comparison 221, 222 103 abuse comparison 218,219 caffeinism 80,81 onset of action 99 continuous therapy 259 oral clefts 262 definition 201 oxazepam abuse comparison 219-21 WHO 181 pentobarbital abuse comparison 216-18 dosing 81 pentobarbital withdrawal 202,203 factors affecting 183 prazepam abuse comparison 222 high-dose 235,236 self administration in humans 205,206 importance 179 long-term 206 incidence 78 slow release 47 low, therapeutic dose 203,204,236-42 plasma levels 48 etiologies 237 status epilepticus, regimen 149, 150 sedative-hypnotic withdrawal 242 Third World uses 167-72 signs 245 anesthesis 171, 172 treatment 243,244 eclampsia 171 neonatal 242, 243 emotional disorders 167, 168 physical 112 malaria 169,170 physiological 201, 204 tetanus 168, 169 prone individuals 79,81 use patterns 255 prospective studies need 241, 242 USuse 89 physiological 201,209 DMCM, structure and actions 26-8 evaluation 204 doctor warmth 118 reports 185 dose routes to 184,186 high- and low- designations 243 sedative-hypnotic 235,236,238 international variations 68 244, 245 minimal effective hypnotic 93 treatment 244,245 psychotropic effects 60,61 symptoms and desmethyldiazepam 241 therapeutic withdrawal 96 therapeutic use 182, 183 titration 92-4 Third World and diazepam 172 drug abuse history see a/so abuse types 78,79 and abuse liability 214 WHO Expert Committee 270,273 aftercare 230 and withdrawal 185,204 benzodiazepine reinforcement 209-213 depression drug accumulation 51-4,125 anxiety 113 scheme and effects 52 benzodiazepines 164 drug combinations 74 desmethylclobazam, serum drug companies and education role 263, concentrations 51, 52 264 desmethyldiazepam drug holidays 119 half-life 54 drug interactions, alcohol and plasma levels 48 benzodiazepines 227, 228 dependence symptoms 240,241 drug response assessment 94,95 precursors 54, 98 drug-seeking behaviour 13 diagnostic criteria, anxiolytics 101,102 duration of action diazepam determinants 49-51 abuse 189,258,259 lipophilic properties 50 309 BENZODIAZEPINES duration of action contd classification 61, 94 termination mechanisms 49, 50 hypnotic, clinical comparison 121-40 onset of action 100 eclampsia, mortality and diazepam in plasma clearance rebound 63 Zambia 171 ranges, benzodiazepines 54 education 263, 264 short and tapering 53 endocrine effects 10, 11 and symptom return 100 Europe, benzodiazepine use 72-4 heterocyclic ring variations 71 high pressure liquid chromatography, females and overmedication 2 retention procedure 44 anxiolytic use 255, 256 hypnotics health system use 256 activity onset 124, 125 tranquillizer treatment, reasons 75 adjunctive use 137-40 FG 7142, structure 27 doseandreboundinsomnia 133-5 , alcohol and psychotropic drug dose-titration 93 use 76,77 efficacy 126, 127 flunitrazepam PH] brain binding 22, 23 intermediate term 127,128 flurazepam short term 126, 127 anxiolytic effect 139 half-lives, comparison 125 drug accumulation 139 insomnia 121 effectiveness and sleep 126,127 choice 140 carry-over 132 early morning 129-31 half-life 94 selection 122 and hypnotic use 125 limits to use 92 insomnia, drug of choice 138 long acting 92 use 189 short term efficacy 127 withdrawal and sleep disturbance 136 side effects 127-31 Food and Drugs Administration, structural relationships 89 benzodiazepines introduction 69 withdrawal effects 131-7 , benzodiazepine availability 70 Iceland, benzodiazepine use 72 GABA see (:I-aminobutyric acid indications 67, 68, 87, 89 GABAergic action, benzodiaepines 7 anxiolyticuse 101,102 GABAergic neurons DSM-IlI diagnostic criteria 10 1, 102 firing facilitation 34 proper use 90, 91 interneurons 15 insomnia 10 presynaptic inhibition 16 actual sleep 90 wiring diagrams 14 alcohol use 123 GABAergic transmission, benzodiazepine description 123 effects 16, 17 drug history 124 potentiation 32 drug-induced 123 selflimiting 33,34 drug aggravating 91 GABA-facilitation mechanism 17 early morning 125,129-31 GABA potentiation non-drug management 91 andCNSactivity 19 prescribing 121 intensity 33 prevalence 122 GABA synapse psychiatricfactors 124 benzodiazepineaction 13-19,33 rebound 123,124,132 postsynaptic inhibition 15 dose 133-5 generic names 287-304 drugs causing 132-4, 136 , benzodiazepine availability 70 and metabolism 135 Gilbert's syndrome 55 treatment and 124, 125 adjunctive and hypnotics 137-40 halazepam international legislation and control 268-71 abuse 221 application, variability 275,276 half-life 97,98 assessment 280,281 half-lives cost/benefit outlines 278,279 and accumulation 51-4 environmental factors 270 anxiolytic 97, 98 psychotropics inclusion 271-3 310 INDEX

relevance 277,278 nitrazepam rights 276,277 abuse 189 therapeutic use 275 rebound insomnia 132 international use seizure use 153 anxiety level 74,75 nocturnal myoclonus 164 defined daily doses 71-3 , psychotropic drug use 72,73 illness-treatment fit 74 numbers of benzodiazepines synthesized , benzodiazepine availability 70 oral clefts and diazepam in 262, , benzodiazepineavailability 70 263 overdose 228 lipid 43,44 acute, data 256-8 lithium 163 mortality, diazepam 257,258 microsomal enzymes 117 overmedication 251 long-term use 78 disorder prevalence and use 252 anxiolytic 102-4 US assessment 254 concern 183 overuse, definition 181 postcoronary 103 oxazepam users 253 abuse and diazepam 219-21 lorazepam dose 100 abuse 221,222 half-life 97,98, 100 cardiorespiratory depression 151 oxidative pathways dependence 80 clinical effects 55,56 duration of action 51 factors affecting 55 half-life 97,98 status epilepticus 151, 152 pain, physical and psychic 90 lormetazepam, rebound insomnia 132 panic disorder 10 1 paradoxical rage reaction 194, 229, 230 malaria see also chloroquine pentobarbital cerebral and diazepam 169, 170 benzodiazepam abuse comparison 216-19 doses 170 diazepam withdrawal 202,203 management, non-drug 91 peripherally acting benzodiazepines 23 mania and clonazepam use 166 pharmacodynamics, benzodiazepine media differences 100 dependence 180 pharmacokinetics 43-56 Valium 251,258 blood levels and brain dynamics 70 memory impairmeqt 129 chronic anxiety treatment 59-64 metabolism and age 227 international views 69 methadone 161 pharmacological actions 7-13, 99-101 methaqualone abuse 184,193 pentobarbital withdrawal treatment 246 midazolam , benzodiazepine abuse elimination 50 comparison 215,216 rebound insomnia 132 phobia 113 misuse 77 , 89, 90 photoaffinity labelling 23 definition 181 physico-chemical properties 43-5 hypnotics, by physicians 121, 122 placebo effect long-term use 78 benzodiazepine abuse comparison 215 motor impairment 228,229 and hypnotics 94 Multiple Sleep Latency Test 130 plasma clearance and half-lives 63 4, 89 plasma levels clinical improvement 102 National Ambulatory Medical Care Survey invasion kinetics 59-62 (NAMCS) 253 plateau and half-lives 61,62 neonate, 242,243 steady-state concentration 55,56 neurochemical probes 1 plasma protein binding 44,45 neurons see also GABA prazepam benzodiazepine targets 18, 19 abuse 222 secondary targets 19 half-life 97, 911 neurotransmission, benzodiazepines 13,14

311 BENZODIAZEPINES prazepam physiological role 32 uses 48 rebound 95 prescribing practices 75 receptors, GABA anxiety and risks 116 antagonists 16 sex bias 255 benzodiazepine receptor model 31 social solutions 76 chloride channel proteins 15, 30, 31 prescription -effector mechanisms 18 control, removal from 82 types and activities 16 guidelines in anxiety 118, 119 receptor, nicotinic cholinoceptor 20 rate, women 75,76 regulation 263 refusal 119 reinforcing properties and drug presynaptic inhibition abuse 210-13 diazepam 13 relapse rates, anxiety treatment 103 spinal cord 16 restless leg~ 164 Profile of Mood States (POMS) 114 RO 15-1788 propranolol action 30 anxiety 117, 118 benzodiazepine receptor block 13,23 withdrawal strategy 244-6 properties 25, 26 psychiatric morbidity structural formula 25 incidence 74 withdrawal precipitation 240 third world drug use 167, 168 tranquillizer use 75 safety 2,81 psychic distress index 75 Schedule IV 263,280 psychosocial stimuli 115 95 psychotherapy and diazepam in anxiety 103 benzodiazepines and GABA activity 163 psychotropic, definition 283 sedative effects 9 seizures 87, 89 see also status epilepticus quazepam withdrawal and sleep alcohol withdrawal 154 disturbance 136 benzodiazepam use 149-55 clonazepam use 152, 153 radioreceptor assay 23 eclamptic treatment 154 rebound phenomena 79 head trauma 154 factors affecting 62,63 menstrual cycle 153 receptors pentylenetetrazol-induced 8 mode of action 20 sleep disturbance 90 properties 19, 20 assessment and drug use 92 supersensitivity and propranolol 95, % hypnotic effectiveness 126,127 receptor, {J -adreno, actions 20 social effects 67 receptor, benzodiazepines 19-32,115,240 abuse 195 adaptation 53 benefits of tranquillizers 76 agonists 28 benzodiazepine, alcohol and 282 inverse 35 implications of use 76 partial and mixed 28,29 social phobias 199 antagonists 25-8 see also individual spasticity 6~, 69 compounds spinal cord, benzodiazepineeffects 16,17 differences 205 Stanford Sleepiness Scale 130 binding sites 20, 240 State Trait Anxiety Index 115 classes 23, 24 status epilepticus 68 derivative affinity 22 clonazepam administration 150, 151 down-regulation 24 diazepam use 149, 150 multiplicity 24 and 150 specific brain 21-4 step-wise 150 {J -carboline effects 26-8 lorazepam use 151 chloride channel complexes 30-3 and depressant combination 231 -effector complexes and stress benzodiazepines 32 features and effects 114 endogenous ligands 29 identification 118 model 29-32 illness 115 complex 30, 31 structure-activity relations 21,87, 88

312 INDEX 138 inclusion criteria 268, 269 , psychotropic drug use 72,73 inclusion process 271-3 symptoms, benzodiazepine withdrawal problems 273-80 syndromes 228,238 United Nations Universal Declaration of Human Rights 276 US, benzodiazepine availability 70,98 Taylor Manifest Anxiety Scale 114 use temazepam cost comparisons 282 absorption 125 international comparisons 253 140 levels and emotional disorders 252 performance 129 principles 90-6 restricted use 138, 139 users 252-4 withdrawal 140 patient patterns 255 tetanus, diazepam use, Third World 168, 169 volume of distribution 50, 51 survival 169 therapeutic applications 87 -96 withdrawal 12 drug discontinuing 95,96 alcohol 89 duration 91,92 benzodiazepines 230,236 therapeuticindex 56 regimens 160, 161 Third World seizures 154 black market 82 barbiturate pretreatment 240 diazepam use see also diazepam 167-72 benzodiazepine 159,160 use 68 short acting 241 tic dulourex, clonazepam 165 symptoms 236 tobacco, benzodiazepine and social convulsions and dose 104 costs 282 definition 159 tolerance II, 12, 104 diazepam dose 112 action termination 50 pentobarbital 202,203 definition 181 in rats 202, 203 drug holidays 119 dose withdrawal reactions 96 toxicity II drug half-life 53,78,79 behavioural 230-3 see also duration of treatment 79,132 behaviour 228-31 effects of sudden 79 trade names 287-304 hypnotics 131-7 see also insomnia, triazolam rebound 131-7 activity onset, intravenous 46 incidence 79, 80 pentobarbital abuse comparison 218 lorazepam 104 rebound insomnia 132 narcotics and benzodiazepine use 188 side-effects and suspension 131 161 withdrawal and sleep disturbance 136, physician support 81 140 receptor blockers 13 abuse comparison 222,223 sedative-hypnotic types 235,236,238 tricyclic antidepressants in anxiety 117 stimulant regimen 161 L-tryptophan and stimulant withdrawal 161 syndromes compared 239 tapering dose 104 UK treatment strategies 243, 244 benzodiazepine availability 70 tricyclic antidepressants 103 psychotropic drug prescribing 72 Women in Crisis Conference 256 United Nations, Division of Mental World Health Organization (WHO) Health 274 abuse classification 182 United Nations Convention on Psychotropic essential drugs 167 Substances (1971) 82,268 data validity 273-5 zopiclone 281

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