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

Table 1. Benzodiazepine research designations with corresponding generic names

Research Designation Generic Name

lactam demoxepam

methyloxazepam temazepam

A 101 nordazepam

AB 35616 clorazepate

AB 39083 clorazepate

AH 3232 clorazepate

CB 4261 tetrazepam

CB 4306 clorazepate

CB 4311 clorazepate

CGS 8216 (antagonist)

CI683 ripazepam

CS 370 cloxazolam

CS 430 haloxazolam

D40TA estazolam

EGYT 341 tofisopam

ER 115 temazepam

HR 158 loprazolam

HR376 clobazam

HR 4723 clobazam

HR930 fosazepam

K3917 temazepam

287

Research Designation

LA 111

LM 2717

ORF 8063

Ro 4-5360

Ro 5-0690

Ro 5-0883

Ro 5-2092

Ro 5-2180

Ro 5-2807

Ro 5-2925

Ro 5-3059

Ro 5-3350

Ro 5-3438

Ro 5-4023

Ro 5-4200

Ro 5-4556

Ro 5-5345

Ro 5-6789

Ro 5-6901

Ro 15-1788

Ro 21-3981

RU 31158

S 1530

SAH 1123

SAH 47603

SB 5833

SCH 12041

SCH 16134

U 28774

U 31889

U 33030

W4020

We 352

THE BENZODIAZEPINES

Generic Name

diazepam

clobazam

triflubazam

nitrazepam

chlordiazepoxide

desmethy1chlordiazepoxide

demoxepam

desmethyldiazepam

diazepam

desmethylmedazepam

nitrazepam

bromazepam

fludiazepam

clonazepam

flunitrazepam

medazepam

temazepam

oxazepam

flurazepam

(antagonist)

midazolam

loprazolam

nimetazepam

isoquinazepam

temazepam

camazepam

halazepam

quazepam

ketazolam

alprazolam

triazolam

prazepam

triflubazam

288

RESEARCH, GENERIC AND TRADE NAMES

Research Designation Generic Name

We 941 brotizolam

Wy 2917 temazepam

Wy 3467 diazepam

Wy 3498 oxazepam

Wy 3917 temazepam

Wy 4036 lorazepam

Wy 4082 lormetazepam

Wy 4426 oxazepam

Y 6047 ciotiazepam

Table 2. Benzodiazepine generic names with corresponding trade names

Generic Name

alprazolam

bromazepam

brotizolam

camazepam

chlordiazepoxide

c10bazam

Trade Name(s)

Xanax

Compendium, Lectopam, Lexatin, Lexomil, Lexotan, Lexotanil

Lendorm, Lendormin

Albego, Limpidon, Paxor

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, Reposal, Relaxil, Reliberan, Risachief, Risolid, Seren, Silibrin, Sintesedan, Smail, Solium, SonimenTrilium, Tropium, Viansin, Zeisin, Zetran

Castilium, Frisin, Frisium, Karidium, Noiafren, Sentil, Urbadan, Urbanol, Urbanyl

289

Generic Name

clonazepam

clorazepate

clorazolam

clotiazepam

cloxazolam

diazepam

estazolam

fiudiazepam

fiunitrazepam

THE BENZODIAZEPINES

Trade Name(s)

Clonopin, Iktorivil, Landsen, Rivotril

Azene, Belseren, Covengar, Enadine, Justum, Mendon, Moderane, Nansius, Tencilan, Transene, Tranxen, Tranxene, Tranxilen, Tranxilene, Tranxilium, Uni-Tranxene

see triazolam

Rize, Trecalmo

Enadel, Lubalix, OIcadil, Sepazon, Tolestan

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

Domnamid, Esilgan, Eurodin, Nuctalon

Erispan

Darkene, Narcozep, Primun, Rohipnol, Rohypnol, Roipnal, Val sera

290

Generic Name

flurazepam

flutazolam

halazepam

haloxazolam

ketazolam

loprazolam

lorazepam

lormetazepam

medazepam

mexazolam

midazolam

nimetazepam

RESEARCH, GENERIC AND TRADE NAMES

Trade Name(s)

Benozil, Dalmane, Dalmadorm, Dalmate, Domodor, Dormodor, Felison, Felmane, Flunox, Fordrim, Insumin, Lunipax, Midorm AR, Natam, Niotal, Remdue, Somlan, Valdorm

Coreminal

Paxipam

Some lin

Anxon, Contamex, Loftran, Solatran, Unakalm

Avlane, Dormonoet

Almazine, Aplaeasse, Ativan, Control, Emotieal, Emotival, Kalmalin, Loraus, Lorax, Lorsilan, Lorenin, NIC, Orfidal, Plaeidia, Psieopax, Quait, Seeurit, Sedarkey, Sedatival, Sidenar, Tavor, Temesta, Trapax, Wypax

Loramet, Noetamid

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

Dormieum

Elimin, Erimin, Hypnon

291

Generic Name

nitrazepam

nordazepam

oxazepam

oxazolam

oxazolazepam

pinazepam

prazepam

temazepam

tetrazepam

tofisopam

tofizopam

triazolam

THE BENZODIAZEPINES

Trade Name(s)

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

Calmday, Demadar, Madar, Stilny

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

see oxazolam

Domar, Duna

Centrax, Demetrin, Equipaz, Lysanxia, Mono Demetrin, Prazene, Reapam, Sedapran, Trepidan, Verstran

Cerepax, Euhypnos, Lenal, Levanxene, Levanxol, Mabertin, Maeva, Normison, Planum, Remestan, Restoril, Signopam

Clinoxan, Musaril, Myolastan

Grandaxin, Grandaxine, Seriel

see tofisopam

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

Trade Name

Diaceplex

Diapam

Diatran

Diazemuls

Diazepina

Diepin

Dipam

Dipezona

Disarim

Domar

Domnamid

Domordor

Dormicum

Dormodor

Dormonoct

Doval

Drenian

D-Tran

Ducene

Dumolid

Duna

Eatan

Eden-psich

Edenquil

Elbrus

Elenium

Elimin

Emotical

Emotival

Enadel

Enadine

Enidrel

E-Pam

RESEARCH, GENERIC AND TRADE NAMES

Generic Name

diazepam

diazepam

diazepam

diazepam

chlordiazepoxide

medazepam

diazepam

diazepam

chlordiazepoxide

pinazepam

estazolam

flurazepam

midazolam, nitrazepam

flurazepam

loprazolam

diazepam

diazepam

diazepam

diazepam

nitrazepam

pinazepam

nitrazepam

chlordiazepoxide

chlordiazepoxide

medazepam

chlordiazepoxide

nimetazepam

lorazepam

lorazepam

cloxazolam

clorazepate

oxazepam

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

Trade Name

Justum

Kalmalin

Karidium

Klopoxid

Labican

Landsen

Lectopam

Lembrol

Lenal

Lendorm

Lendormin

Lerisum

Levanxene

Levanxol

Levium

Lexatin

Lexomil

Lexotan

Lexotanil

Liberans

Limbial

Librium

Libritabs

Limpidon

Lixin

Loftran

Loramet

Loraus

Lorax

Lorinon

Lorsilan

Lorenin

Lubalix

RESEARCH, GENERIC AND TRADE NAMES

GenericName

c10razepate

lorazepam

c10bazam

chlordiazepoxide

chlordiazepoxide

c10nazepam

bromazepam

diazepam

temazepam

brotizolam

brotizolam

medazepam

temazepam

temazepam

diazepam

bromazepam

bromazepam

bromazepam

bromazepam

chlordiazepoxide

oxazepam

chlordiazepoxide

chlordiazepoxide

camazepam

chlordiazepoxide

ketazolam

lormetazepam

lorazepam

lorazepam

diazepam

lorazepam

lorazepam

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

Trade Name

Neo-Calme

Nesontil

Neuchlonic

Neurolytril

NrC

Niotal

Nipam

Nitrados

Nitrenpax

Nivelton

Noan

Nobrium

Noctamid

Noctene

Noiafren

Normide

Normison

Notense

Novodipam

Novopoxide

Nuctalon

Nulans

O.C.M.

Okadil

Omnalio

Orfidal

Oxadin

Oxepam

Pacisyn

Pacitran

Pax

Paxate

Paxel

RESEARCH, GENERIC AND TRADE NAMES

Generic Name

diazepam

oxazepam

nitrazepam

diazepam

lorazepam

flurazepam

nitrazepam

nitrazepam

nitrazepam

medazepam

diazepam

medazepam

lormetazepam

nitrazepam

clobazam

chlordiazepoxide

temazepam

diazepam

diazepam

chlordiazepoxide

estazolam

oxazepam

chlordiazepoxide

cloxazolam

chlordiazepoxide

lorazepam

oxazepam

oxazepam

nitrazepam

diazepam

diazepam

diazepam

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

Trade Name

Relanium

Relaxil

Reliberan

Relivan X

Remdue

Remestan

Remnos

Resmit

Restoril

Risachief

Risolid

Rivotril

Rize

Rohipnol

Rohypnol

Roipnal

Rudotel

Saromet

Scriptopam

Securit

Sedapam

Sedapran

Sedaril

Sedarkey

Sedativil

Sedokin

Seduxen

Sentil

Sepazon

Serax

Seren

Serenack

Serenal

RESEARCH, GENERIC AND TRADE NAMES

Generic Name

diazepam

chlordiazepoxide

chlordiazepoxide

diazepam

flurazepam

temazepam

nitrazepam

medazepam

temazepam

chlordiazepoxide

chlordiazepoxide

clonazepam

clotiazepam

flunitrazepam

flunitrazepam

flunitrazepam

medazepam

diazepam

diazepam

lorazepam

diazepam

prazepam

diazepam

lorazepam

lorazepam

oxazepam

diazepam

clobazam

cloxazolam

oxazepam

chlordiazepoxide

diazepam

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

Trade Name

Stilny

Surem

Tavor

Temesta

Templane

Tencilan

Tensium

Tolestan

Tranimul

Tranquase

Tranquilax

Tranquirit

Tranquit

Tranquo-Tablinen

Transene

Tranxen

Tranxene

Tranxilen

Tranxilene

Tranxilium

Trapax

Trecalmo

Trepidan

Trilium

Tropium

Unakalm

Unisomnia

Uni-Tranxene

Urbadan

Urbanol

Urbanyl

Valdorm

Valitran

RESEARCH, GENERIC AND TRADE NAMES

Generic Name

nordazepam

nitrazepam

lorazepam

lorazepam

medazepam

clorazepate

diazepam

cloxazolam

diazepam

diazepam

medazepam

diazepam

oxazolam

diazepam

clorazepate

clorazepate

clorazepate

clorazepate

clorazepate

clorazepate

lorazepam

clotiazepam

prazepam

chlordiazepoxide

chlordiazepoxide

ketazolam

nitrazepam

clorazepate

clobazam

clobazam

clobazam

flurazepam

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, Abuse. 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 Drug Abuse, 1981.

305

Index

absorption rates factors affecting 49 hypnotics 122, 124, 125, oral benzodiazepines 46-8

abuse 35,36 behavioral effects 193,194

negative 193 benzodiazepine avoidance 95 benzodiazepines used 189, 190

new 190 cortical atrophy 194 definition 181 and dependence differences 194,195 diazepam, Third World 172 disorder classification 181 experimental assessment 201-7

drug abuse 210-14 human self-administration 205,206 human studies 209-23 phenothiazine comparison 215 placebo comparison 215

forecasting potential 191-3 animal studies 191 human volunters 191-3

international legislation 269-71 liability 202 mUltiple 186,187 potential 2, 117 primary 103-6

international data 184 secondary 179,186-90,194,195

and alcohol 186 euphoriant 189 narcotics and 187 reasons and narcotics 188, 189 urine test 187

socio-medical appraisal 195 street cost 188 Switzerland, drug incidence 186

activity onset 45-9,99 and hypnotic use 124,125

intravenous 46 oral 46-8

adaptation 52 addiction see dependence, abuse and

withdrawal adverse drug reactions 2 see also tolerance,

toxicity, dependence and withdrawal amnesia 10 behavioral 131 and benzodiazepine abuse 95 clobazam 154 clonazepam 165 eNS depressant 99 early morning insomnia 129-31 fiurazepam 139 hangover 49 hypnotics 127-31

daytime sedation 127-9 memory 129

initial treatment 53,60 metabolism 102 performance 10 psychotropic 60 sedation 93,117 social 76 temazepam 140 tricyclic antidepressants 117 triazolam 131, 139 tryptophan 161

aggression enhancement 100,101 reduction 9

alcohol use and abuse anxiety 112

307

benzodiazepine reinforcement 210,212, 213

benzodiazepine social cost 282 cross-tolerance 93, 95 psychotropic drugs 76,77 withdrawal 159-65

alprazolam, half-life 97,98

BENZODIAZEPINES

American Psychiatric Association, abuse classification 181,182

'Y aminobutyric acid see also GABA agonists 16 CNSroie 7 inhibitory neurotransmission 14 presynaptic inhibition 14

amnesia, anterograde 10 anesthesia 88, 165

diazepam in Third World 171, 172 animal studies

abuse potential 191 self-administration 205

anti-anxiety drugs overprescription III sex bias and use 255,258 structures 88 synonyms 112

anticonvulsant activity 7, 8 neuronal activities 34

antiepileptic action 34 anxiety

acute and chronic 113,114 assessment 114 benzodiazepinetherapy 253,254 benzodiazepine use III causes 115 and change 116 chronic treatment 59-64 daytime 129,133 definitions 112, 113 non-psychotic 97 non-psychotropic treatment 112 physician response III rebound 242 treatment 116, 117

!3-blockers 117, 118 guidelines 118, 119 tricyclic antidepressants 117

views of III anxiolytic effects

benzodiazepines 97-105 mechanism 34,35 non-sedative role 10

area under the time-action curve 218 assessment

anxiety 114 benzodiazepine uses 284

autonomic affects 10, 11 autoradiography, benzodiazepine binding

sites 21,22

barbiturates, benzodiazepine receptor actions 30

Beck Depression Scale 115 behavioral effects

anti punishment 9 exploratory 9

behavioral inhibition system 35

behavioral tests, anxiolytic 9 behavioral toxicity 228-31 see also toxicity benefit/cost aspects, drug controls 278,279 benefit/risk ratio 116 Benzodiazepine Research and Training

Project 3 bicuculline 16 binding sites

CNS 21-4 and receptors 24

blood-brain barrier 45 brain regions and benzodiazepine effects 17 brain stem, benzodiazepine effects 17 breast milk, infant drug exposure 228 bromazepam abuse 190

caffeinism 80 anxiety 115 tranquilo-sedative use 80

cancer risk and diazepam use 260,261 cerebellar cortex, benzodiazepine effects 17 cerebral cortex 17 !3-CCE, benzodiazepine antagonism 26,27 !3-CCM, benzodiazepine antagonist 26,27 !3-CCPr, benzodiazepine antagonism 26,27 central nervous system, onset of effects and

plasma invasion 60 CGS 8216, receptor blocking 26 chlordiazepoxide

abuse 189,221 alcohol withdrawal 160,161 anxiolytic half-life 97,98 discovery 1 eclamptic seizures 154 pentobarbital abuse comparison 218

chloroquine toxicity incidence 170,171 mortality and diazepam 170, 171

cimetidine alcohol withdrawal 160 diazepam interaction 56

cirrhosis and clearance 56 clobazam

anticonvulsant use 153 serum concentrations 5 I

clonazepam anticonvulsant interaction 152 gradual onset 152 mania 164 status epilepticus 150, 15 I

clorazepate abuse 222 half-life, anxiolytic 97,98 seizure use 153

cocaine 231 cognitive impairment 229 commercial availability, international

comparison 69,70 conjugation, factors affecting 55,56

308

controls international 268,269 local, psychotropics 267,268

convulsions, electroshock-induced 8 cross-dependence 202 cross-tolerance 93,95 crutch phenomena 79, 183

daytime sedation 127-9 defined daily dose 71-3 dependence 11, 12 see a/so withdrawal

and alcoholism 179, 241 animal studies 203 anxiolytics 103 caffeinism 80,81 continuous therapy 259 definition 201

WHO 181 dosing 81 factors affecting 183 high-dose 235,236 importance 179 incidence 78 low, therapeutic dose 203,204,236-42

etiologies 237 sedative-hypnotic withdrawal 242 signs 245 treatment 243,244

neonatal 242, 243 physical 112 physiological 201, 204 prone individuals 79,81 prospective studies need 241, 242 physiological 201,209

evaluation 204 reports 185 routes to 184,186 sedative-hypnotic 235,236,238

propranolol 244, 245 treatment 244,245

symptoms and desmethyldiazepam 241 therapeutic use 182, 183 Third World and diazepam 172 types 78,79 WHO Expert Committee 270,273 and withdrawal 185,204

depression anxiety 113 benzodiazepines 164

desmethylclobazam, serum concentrations 51, 52

desmethyldiazepam half-life 54 plasma levels 48

dependence symptoms 240,241 precursors 54, 98

diagnostic criteria, anxiolytics 101,102 diazepam

abuse 189,258,259

INDEX

309

anxiolytic half-life 97,98 biotransformations 55 and cancer 260,261 chlordiazepoxide abuse comparison 221 chlorpromazine abuse comparison 215,

216 clorazepate abuse comparison 222 conditions prescribed 254 eclamptic seizures 154 halazepam abuse comparison 221 initial response and outcome 102 life saving 165 lorazepam abuse comparison 221, 222 methaqualone abuse comparison 218,219 onset of action 99 oral clefts 262 oxazepam abuse comparison 219-21 pentobarbital abuse comparison 216-18 pentobarbital withdrawal 202,203 prazepam abuse comparison 222 self administration in humans 205,206

long-term 206 slow release 47

plasma levels 48 status epilepticus, regimen 149, 150 Third World uses 167-72

anesthesis 171, 172 eclampsia 171 emotional disorders 167, 168 malaria 169,170 tetanus 168, 169 use patterns 255 USuse 89

DMCM, structure and actions 26-8 doctor warmth 118 dose

high- and low- designations 243 international variations 68 minimal effective hypnotic 93 psychotropic effects 60,61 therapeutic withdrawal 96 titration 92-4

drug abuse history see a/so abuse and abuse liability 214 aftercare 230 benzodiazepine reinforcement 209-213

drug accumulation 51-4,125 scheme and effects 52

drug combinations 74 drug companies and education role 263,

264 drug holidays 119 drug interactions, alcohol and

benzodiazepines 227, 228 drug response assessment 94,95 drug-seeking behaviour 13 duration of action

determinants 49-51 lipophilic properties 50

BENZODIAZEPINES

duration of action contd termination mechanisms 49, 50

eclampsia, mortality and diazepam in Zambia 171

education 263, 264 endocrine effects 10, 11 Europe, benzodiazepine use 72-4

females and overmedication 2 anxiolytic use 255, 256 health system use 256 tranquillizer treatment, reasons 75

FG 7142, structure 27 Finland, alcohol and psychotropic drug

use 76,77 flunitrazepam PH] brain binding 22, 23 flurazepam

anxiolytic effect 139 drug accumulation 139 effectiveness and sleep 126,127

carry-over 132 half-life 94

and hypnotic use 125 insomnia, drug of choice 138 use 189 withdrawal and sleep disturbance 136

Food and Drugs Administration, benzodiazepines introduction 69

France, benzodiazepine availability 70

GABA see (:I-aminobutyric acid GABAergic action, benzodiaepines 7 GABAergic neurons

firing facilitation 34 interneurons 15 presynaptic inhibition 16 wiring diagrams 14

GABAergic transmission, benzodiazepine effects 16, 17

potentiation 32 selflimiting 33,34

GABA-facilitation mechanism 17 GABA potentiation

andCNSactivity 19 intensity 33

GABA synapse benzodiazepineaction 13-19,33 postsynaptic inhibition 15

generic names 287-304 Germany, benzodiazepine availability 70 Gilbert's syndrome 55

halazepam abuse 221 half-life 97,98

half-lives and accumulation 51-4 anxiolytic 97, 98

classification 61, 94 hypnotic, clinical comparison 121-40 onset of action 100 plasma clearance rebound 63 ranges, benzodiazepines 54 short and tapering 53 and symptom return 100

heterocyclic ring variations 71 high pressure liquid chromatography,

retention procedure 44 hypnotics

activity onset 124, 125 adjunctive use 137-40 doseandreboundinsomnia 133-5 dose-titration 93 efficacy 126, 127

intermediate term 127,128 short term 126, 127

half-lives, comparison 125 insomnia 121

choice 140 early morning 129-31 selection 122

limits to use 92 long acting 92 short term efficacy 127 side effects 127-31 structural relationships 89 withdrawal effects 131-7

Iceland, benzodiazepine use 72 indications 67, 68, 87, 89

anxiolyticuse 101,102 DSM-IlI diagnostic criteria 10 1, 102 proper use 90, 91

insomnia 10 actual sleep 90 alcohol use 123 description 123 drug history 124 drug-induced 123 drug aggravating 91 early morning 125,129-31 non-drug management 91 prescribing 121 prevalence 122 psychiatricfactors 124 rebound 123,124,132

dose 133-5 drugs causing 132-4, 136 and metabolism 135

treatment and pharmacokinetics 124, 125 adjunctive and hypnotics 137-40

international legislation and control 268-71 application, variability 275,276 assessment 280,281

310

cost/benefit outlines 278,279 environmental factors 270 psychotropics inclusion 271-3

relevance 277,278 rights 276,277 therapeutic use 275

international use anxiety level 74,75 defined daily doses 71-3 illness-treatment fit 74

Italy, benzodiazepine availability 70

Japan, benzodiazepineavailability 70

lipid solubility 43,44 lithium 163 liver microsomal enzymes 117 long-term use 78

anxiolytic 102-4 concern 183 postcoronary 103 users 253

lorazepam abuse 221,222 cardiorespiratory depression 151 dependence 80 duration of action 51 half-life 97,98 status epilepticus 151, 152

lormetazepam, rebound insomnia 132

malaria see also chloroquine cerebral and diazepam 169, 170

doses 170 management, non-drug 91 mania and clonazepam use 166 media

dependence 180 Valium 251,258

memory impairmeqt 129 metabolism and age 227 methadone 161 methaqualone abuse 184,193 midazolam

elimination 50 rebound insomnia 132

misuse 77 , 89, 90 definition 181 hypnotics, by physicians 121, 122 long-term use 78

motor impairment 228,229 Multiple Sleep Latency Test 130 muscle relaxant 4, 89

National Ambulatory Medical Care Survey (NAMCS) 253

neonate, physical dependence 242,243 neurochemical probes 1 neurons see also GABA

benzodiazepine targets 18, 19 secondary targets 19

neurotransmission, benzodiazepines 13,14

INDEX

nitrazepam abuse 189 rebound insomnia 132 seizure use 153

nocturnal myoclonus 164 Norway, psychotropic drug use 72,73 numbers of benzodiazepines synthesized

oral clefts and diazepam in pregnancy 262, 263

overdose 228 acute, data 256-8 mortality, diazepam 257,258

overmedication 251 disorder prevalence and use 252 US assessment 254

overuse, definition 181 oxazepam

abuse and diazepam 219-21 dose 100 half-life 97,98, 100

oxidative pathways clinical effects 55,56 factors affecting 55

pain, physical and psychic 90 panic disorder 10 1 paradoxical rage reaction 194, 229, 230 pentobarbital

benzodiazepam abuse comparison 216-19 diazepam withdrawal 202,203

peripherally acting benzodiazepines 23 pharmacodynamics, benzodiazepine

differences 100 pharmacokinetics 43-56

blood levels and brain dynamics 70 chronic anxiety treatment 59-64 international views 69

pharmacological actions 7-13, 99-101 pentobarbital withdrawal treatment 246 phenothiazines, benzodiazepine abuse

comparison 215,216 phobia 113 photoaffinity labelling 23 physico-chemical properties 43-5 placebo effect

benzodiazepine abuse comparison 215 and hypnotics 94

plasma clearance and half-lives 63 plasma levels

clinical improvement 102 invasion kinetics 59-62 plateau and half-lives 61,62 steady-state concentration 55,56

plasma protein binding 44,45 prazepam

abuse 222 half-life 97, 911

311

BENZODIAZEPINES

prazepam coma uses 48

prescribing practices 75 anxiety and risks 116 sex bias 255 social solutions 76

prescription control, removal from 82 guidelines in anxiety 118, 119 rate, women 75,76 refusal 119

presynaptic inhibition diazepam 13 spinal cord 16

Profile of Mood States (POMS) 114 propranolol

anxiety 117, 118 withdrawal strategy 244-6

psychiatric morbidity incidence 74 third world drug use 167, 168 tranquillizer use 75

psychic distress index 75 psychosocial stimuli 115 psychotherapy and diazepam in anxiety 103 psychotropic, definition 283

quazepam withdrawal and sleep disturbance 136

radioreceptor assay 23 rebound phenomena 79

factors affecting 62,63 receptors

mode of action 20 properties 19, 20 supersensitivity and propranolol 95, %

receptor, {J -adreno, actions 20 receptor, benzodiazepines 19-32,115,240

adaptation 53 agonists 28

inverse 35 partial and mixed 28,29

antagonists 25-8 see also individual compounds

barbiturate differences 205 binding sites 20, 240

classes 23, 24 derivative affinity 22 down-regulation 24 multiplicity 24 specific brain 21-4

{J -carboline effects 26-8 chloride channel complexes 30-3 -effector complexes and

benzodiazepines 32 endogenous ligands 29 model 29-32

complex 30, 31

physiological role 32 rebound 95

receptors, GABA antagonists 16 benzodiazepine receptor model 31 chloride channel proteins 15, 30, 31 -effector mechanisms 18 types and activities 16

receptor, nicotinic cholinoceptor 20 regulation 263 reinforcing properties and drug

abuse 210-13 relapse rates, anxiety treatment 103 restless leg~ 164 RO 15-1788

action 30 benzodiazepine receptor block 13,23 properties 25, 26 structural formula 25 withdrawal precipitation 240

safety 2,81 Schedule IV 263,280 schizophrenia 95

benzodiazepines and GABA activity 163 sedative effects 9 seizures 87, 89 see also status epilepticus

alcohol withdrawal 154 benzodiazepam use 149-55 clonazepam use 152, 153 eclamptic treatment 154 head trauma 154 menstrual cycle 153 pentylenetetrazol-induced 8

sleep disturbance 90 assessment and drug use 92 hypnotic effectiveness 126,127

social effects 67 abuse 195 benefits of tranquillizers 76 benzodiazepine, alcohol and tobacco 282 implications of use 76

social phobias 199 spasticity 6~, 69 spinal cord, benzodiazepineeffects 16,17 Stanford Sleepiness Scale 130 State Trait Anxiety Index 115 status epilepticus 68

clonazepam administration 150, 151 diazepam use 149, 150

and phenytoin 150 step-wise 150

lorazepam use 151 stimulant and depressant combination 231 stress

features and effects 114 identification 118 illness 115

structure-activity relations 21,87, 88

312

INDEX

suicide 138 Sweden, psychotropic drug use 72,73 symptoms, benzodiazepine withdrawal

syndromes 228,238

Taylor Manifest Anxiety Scale 114 temazepam

absorption 125 anterograde amnesia 140 performance 129 restricted use 138, 139 withdrawal 140

tetanus, diazepam use, Third World 168, 169

survival 169 therapeutic applications 87 -96

drug discontinuing 95,96 duration 91,92

therapeuticindex 56 Third World

black market 82 diazepam use see also diazepam 167-72 use 68

tic dulourex, clonazepam 165 tobacco, benzodiazepine and social

costs 282 tolerance II, 12, 104

action termination 50 definition 181 drug holidays 119

toxicity II behavioural 230-3 see also

behaviour 228-31 trade names 287-304 triazolam

activity onset, intravenous 46 pentobarbital abuse comparison 218 rebound insomnia 132 side-effects and suspension 131 withdrawal and sleep disturbance 136,

140 zopiclone abuse comparison 222,223

tricyclic antidepressants in anxiety 117 L-tryptophan and stimulant withdrawal 161

UK benzodiazepine availability 70 psychotropic drug prescribing 72

United Nations, Division of Mental Health 274

United Nations Convention on Psychotropic Substances (1971) 82,268

data validity 273-5

inclusion criteria 268, 269 inclusion process 271-3 problems 273-80

United Nations Universal Declaration of Human Rights 276

US, benzodiazepine availability 70,98 use

cost comparisons 282 international comparisons 253 levels and emotional disorders 252 principles 90-6

users 252-4 patient patterns 255

volume of distribution 50, 51

withdrawal 12 alcohol 89

benzodiazepines 230,236 regimens 160, 161 seizures 154

barbiturate pretreatment 240 benzodiazepine 159,160

short acting 241 symptoms 236

convulsions and dose 104 definition 159 diazepam dose 112

pentobarbital 202,203 in rats 202, 203

dose withdrawal reactions 96 drug half-life 53,78,79 duration of treatment 79,132 effects of sudden 79 hypnotics 131-7 see also insomnia,

rebound 131-7 incidence 79, 80 lorazepam 104 narcotics and benzodiazepine use 188 opiate 161 physician support 81 receptor blockers 13 sedative-hypnotic types 235,236,238 stimulant regimen 161 syndromes compared 239 tapering dose 104 treatment strategies 243, 244 tricyclic antidepressants 103

Women in Crisis Conference 256 World Health Organization (WHO)

abuse classification 182 essential drugs 167

zopiclone 281

313