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