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Anesthetics, General
→ Local Anesthetics is a separate keyword.
in blood pressure and body temperature, on- less soluble in blood and require a higher par-
set of hypoxemia, cyanosis tial pressure to maintain the tolerance stage. The
steep concentration gradient makes it possible
During emergence from the tolerance stage, to induce and withdraw anesthesia quickly, thus
the patient passes back through the excitation providing better control of the narcosis.
and analgesia stages. The “minimum alveolar concentration”
Effective anesthesia is required to bring (MAC), a concept introduced in 1965, is a mea-
about sure of the potency of inhalation anesthetics. It
is expressed as the concentration in the alveo-
1) Unconsciousness lar air that prevents 50 % of patients from re-
2) Complete analgesia and absence of pain re- sponding to pain stimuli. The MAC levels are
flexes changed by premedication agents or adjuncts,
3) Relaxation of the muscles and anesthetic dosage always must be adjusted
accordingly. However, the concentration of an
The patient must receive sufficient anesthetic anesthetic agent cannot be increased arbitrarily
to fulfill the third requirement; in practice, this because of the narrow therapeutic range, which
usually means overdosage regarding the first two for most agents is ≈ 1.5.
requirements. Consequently, a combined tech-
nique is currently in use: other pharmaceutical Intravenous (Parapulmonary) Anesthet-
agents, generally sedatives, neuroleptics, anal- ics. Metabolization and distribution gradually
gesics, and muscle relaxants, are used to support render intravenous agents ineffective; i.e., they
the anesthesia, particularly in the initial phase. are subject to processes over which the anesthe-
Depending on the duration of their action, siologist has no influence. Further, these agents
anesthetic agents are termed long acting, short cannot be controlled once they have been ad-
acting, or very short acting. Depending on how ministered. However, they are psychologically
they are administered, they also can be divided well tolerated by patients, and they are quite use-
into inhalation, intravenous, and combination ful for brief narcosis and as induction agents
anesthetics. for inhalation anesthesia, providing the basic
anesthesia. Only intravenous anesthetics can be
Inhalation (Pulmonary) Anesthetics. A used when the airways must be maintained com-
large number of gases or vapors that are in- pletely patent.
haled in a mixture with air or oxygen produce
unconsciousness and analgesia. For practical Combination Anesthesia. Inhalation or in-
purposes, however, only a few have proved effi- travenous anesthetics, used singly, depend on
cacious. dosage to achieve the conditions necessary for
Inhalation anesthetics are characterized by surgery: autonomic depression, sleep, analge-
great stability. They are taken up quickly in the sia, and muscle relaxation. Nowadays, prefer-
lungs and to a large extent are eliminated rapidly ence is given to combinations of medications,
and mostly unchanged through the lungs (only which broaden the therapeutic range. Moreover,
minimally in the urine). They can be withdrawn with several substances administered at minimal
immediately should an untoward incident occur; dosages the particular goals of anesthesia can be
i.e., they can be controlled. Their main disad- achieved.
vantages are that they often cause a pronounced Sleep-inducing anesthetics. To induce nar-
excitation stage and that many patients expe- cosis and regulate sleep, the short-acting barbitu-
rience discomfort (postnarcotic nausea, vomit- rates (the induction agents) – etomidate, steroid
ing). With inflammable gases the danger of ex- anesthetics, and some benzodiazepine deriva-
plosion is always present. tives – are used.
Gas and vapor anesthetics exhibit different Neuroleptanalgesics. A stage that approxi-
distributions between the lipophilic and hy- mates that reached during the first stage of anes-
drophilic phases and so have different solubil- thesia can be attained by simultaneous admin-
ities in blood and different affinities to the lipid- istration of a potent analgesic and a neurolep-
rich nervous tissue of the CNS. The gases are tic agent. In this state of so-called neurolep-
Anesthetics, General 3
tanalgesia, there are complete analgesia, psychic not be achieved with it alone, it is used mixed
and motoric depression, and amnesia. The auto- with oxygen and ether or halothane as a basic
nomic nervous system is depressed, whereas all anesthetic for all types of surgery because of its
important reflexes are retained. In general, the minimal toxicity. Further, N2 O does not irritate
patient remains conscious, making this type of the airways. Nitrous oxide is always mixed with
narcosis particularly suitable for operations in oxygen (20 %, in dentistry 20 – 50 %) to avoid
which active participation on the part of the pa- anoxia. The use of nitrous oxide considerably
tient is necessary, for example, brain, ear, and reduces the requirements for other anesthetics
laryngeal operations. If higher doses of anal- and analgesics.
gesics are given, artificial respiration is nec- Trade Names. Stickoxydul (Hoechst) and oth-
essary. Commonly, the patient is premedicated ers.
with muscle relaxants, such as succinylcholine,
with atropine, and even with anesthetics, such as
propanidid or N2 O–O2 . 2.2. Hydrocarbons
Neuroleptanalgesia is used for gentle narco-
sis, for lengthy operations, or for patients at risk Hydrocarbons have an anesthetic effect. How-
in senium or with cardiovascular diseases. ever, despite their good anesthetic qualities and
Relaxants. Muscular relaxation is necessary low toxicities, they are now rarely used because
for anesthesia and the operation. Some anesthet- of the high risk of explosion. After serious explo-
ics produce muscle relaxation by affecting the sions during anesthesia, ethylene and acetylene
central regulation of the tonus. However, periph- are no longer employed in Germany.
eral muscle relaxation is achieved only by in-
hibiting the neurotransmitter acetylcholine with Cyclopropane [75-19-4], trimethylene,
depolarizing substances or substances that block USP XIX, C3 H6 , M r 42.08, is a colorless, odor-
the acetylcholine receptor in the motor end plate. less, inflammable gas, mp -127 ◦ C, bp −33 ◦ C.
Such relaxants ( → Skeletal Muscle Relaxants) At room temperature it liquefies at 4 – 6 bar
include tubocurarine, alcuronium, gallamine, (400 – 600 kPa). The explosive range is between
pancuronium, decamethonium or suxametho- 2.4 and 10.3 vol % in air and between 12.5 and
nium, neostigmine, and pyridostigmine. Pre- 60.0 vol % in oxygen. The blood – gas partition
medication with the anticholinergics atropine coefficient at 37 ◦ C is 0.46. Cyclopropane is
and scopolamine is common practice. Adminis- mixed with oxygen (15 – 30 % cyclopropane)
tered intramuscularly, these agents inhibit sali- for medical purposes. In contrast to nitrous
vary and gastric secretions (prophylaxis against oxide, cyclopropane (MAC 9.2) at concentra-
aspiration), prevent bradycardia, and provide tions of 20 % can produce anesthesia. It can be
protection against acute vagal reflexes. controlled readily and has a broad therapeutic
range. Cyclopropane increases the sensitivity of
the heart to catecholamines.
2. Inhalation Anesthetics Cyclopropane is manufactured commercially
from 1,3-dichloropropane with zinc in the pres-
2.1. Nitrous Oxide ence of sodium iodide.
Trade Names. Cyclopropane (ICI; Mallinck-
Nitrous oxide [10024-97-2], nitrogen monoxide rodt; Squibb). Cyclopropane USP is available
or laughing gas, N2 O, M r 44.02, is a colorless in sealed orange metal cylinders or in chrome-
gas with a slightly sweet odor and taste, mp – plated cylinders with orange labels.
90.81 ◦ C, bp −88.46 ◦ C. At a pressure of 1 bar
(100 kPa) one volume of water dissolves one vol-
ume of N2 O at 5 ◦ C and 0.596 volumes at 25 ◦ C. 2.3. Halogenated Hydrocarbons
Nitrous oxide also is soluble in alcohol and ether.
For manufacture → Nitric Acid, Nitrous Acid, Low-boiling halogenated hydrocarbons exhibit
and Nitrogen Oxides. anesthetic activity. Compared to hydrocarbons,
Nitrous oxide exerts a shallow anesthetic ef- they are more potent but also more toxic. Anes-
fect, MAC > 80. Although deep anesthesia can- thetics previously in common use – chloroform,
4 Anesthetics, General
carbon tetrachloride, and ethyl chloride – are to considerable accumulation in tissue and fat.
now never or hardly ever employed because of Halothane reduces the peripheral vascular re-
their hepatotoxic and carcinogenic side effects. sistance, increases the possibility of arrythmias,
In addition, tribromoethyl alcohol is no longer and has a negative effect on liver function. On
employed in the major industrial nations. The repeated use it is hepatotoxic.
chlorinated hydrocarbons increase the sensitiv- Trade Names. Fluothane (ICI Pharma);
ity of the heart to catecholamines. Halothan “Hoechst” (Hoechst); Halan
(Arzneimittelwerk Dresden); Halovis (Vister,
Trichloroethylene [79-01-6], CCl2 =CHCl, Italy); Narcotan (Spofa, Prague); Rhodialothan
M r 131.4, is a colorless, noninflammable liquid (Rhodia Pharma).
with a characteristic chloroform-like odor, bp
87.2 ◦ C. (For further information → Chlorinated Teflurane [124-72-1], 2-bromo-1,1,1,2-
Hydrocarbons.) Trichloroethylene is highly hep- tetrafluoroethane, CF3 CHFBr, M r 180.95, a
atotoxic and nephrotoxic and causes hepatocel- nonexplosive, noninflammable gas, bp 8 ◦ C.
lular carcinomas in mice. In the presence of Its anesthetic qualities are similar to those of
alkali, trichloroethylene decomposes to highly halothane [4]. Teflurane is prepared by bromina-
toxic dichloroacetylene and HCl. For anesthetic tion of 1,1,1,2-tetrafluoroethane at temperatures
purposes, the substance is stabilized with thymol above 400 ◦ C [5].
and mixed with a blue coloring agent. Trade Name. Teflurane (Dow; Abbott)
Indication. For inhalation analgesia in ob-
stetrics and for minor surgical procedures, but
only with a special inhaler. Trichloroethylene 2.4. Ethers
(MAC 0.17) should not be used in a closed-
circuit apparatus. Trichloroethylene is better tol- The ethers have a broad anesthetic range; i.e., the
erated than chloroform. difference between the dose needed to produce
Trade Names. Anamenth (Brunnengräber) the tolerance stage and the lethal dose is large.
contains menthol as a stabilizer; Chlorylen They have enjoyed a certain popularity as inhala-
(Schering); Ecrylène (Robert & Carrière, Paris); tion anesthetics. The best known, diethyl ether,
Narkosid (Heyl); Trethylene (Davies-Rose- usually is combined with other agents. There is
Hoyt); Trichloran (Merck); Trilene (ICI; Ay- always the danger of explosion in mixtures with
erst). oxygen or air. The solubility of ether in blood
and tissue results in a 15-min induction period,
Halothane [151-67-7], 2-bromo-2- which is accompanied by irritation of the mu-
chloro1,1,1-trifluoroethane, CF3 CHBrCl, M r cous membranes and airways and by salivation.
197.39, is a colorless, noninflammable liquid The recovery phase is long, and ether is no longer
with a characteristic sweet odor, bp 50.2 ◦ C. in routine use by anesthesiologists, despite its fa-
Halothane is soluble in water to the extent of vorable effects on the bronchial musculature and
0.345 wt %, miscible with ether, and sensitive cardiocirculatory system and its relatively good
to light. Anesthetic halothane contains 0.01 % relaxant effect on the muscles.
thymol as a stabilizer.
Halothane is manufactured by chlorination of Diethyl ether [60-29-7], H5 C2 -O-C2 H5 ,
CF3 CH2 Br or bromination of CF3 CH2 Cl in the M r 74.12, is a mobile, colorless, inflammable
gas phase at 250 – 475 ◦ C [2] or by the rearrange- liquid with characteristic odor, bp 34.6 ◦ C. Mix-
ment [3] tures of diethyl ether and air are explosive. Di-
ethyl ether is miscible with short-chain alcohols,
chloroform, and petroleum ether. An aqueous
solution saturated with ether contains 8.43 wt %
Indication. Because of its potent and rapid ether at 15 ◦ C and 6.05 wt % at 25 ◦ C. Ether
effect, halothane (MAC 0.77) is used in spe- saturated with water contains 1.2 wt % water at
cial vaporizers mixed with oxygen and water. 20 ◦ C (MAC 1.9). For details on preparation and
The high lipid – blood partition coefficient leads purification → Ethers, Aliphatic.
Anesthetics, General 5
Insufficient, frequent side effects: hexobar- cacious for almost 50 years, at least for induction
bital, methitural, buthalital of anesthesia. Abuse can lead to addiction.
Some advantages, some side effects: metho- Trade Names (ampule with dry sub-
hexital, narcobarbital stance): Evipan-Natrium (Bayer); Evipal
Sodium (Winthrop-Stearns); Cyclonal Sodium
Methohexital sodium [309-36-4], sodium (May & Baker); Dorico Solubile (Winthrop);
5-allyl-1-methyl-5-(1-methyl-2-pentynyl)- Hexanastab (Boots); Toleran inj. (Kwizda).
barbiturate, M r 284.30. The free acid
[18652-93-2] forms colorless crystals, mp
60 – 64 ◦ C. It is prepared by condensing di- 3.2. Thiobarbituric Acids
ethyl allyl(1-methyl-2-pentynyl)malonate with
N-methylurea [20]. The anesthetic effect of the thiobarbituric acids
differs from that of the barbiturates in that they
produce a somewhat longer period of sleep after
withdrawal of medication. Emergence is calmer
and quicker. The duration of anesthesia can be
lengthened considerably in patients having only
limited fat deposits outside of the central ner-
Methohexital sodium is a short-acting anes- vous system (i.e., asthenic persons) or having fat
thetic administered intravenously. It is very po- deposits saturated by several injections of thio-
tent and has the shortest duration of action barbiturates. The thiobarbiturates depress respi-
among the barbiturates used. A disturbing factor ration more than the barbiturates and are less
is that rather frequently it causes hiccups directly well tolerated by the veins.
after injection. Patients are reported to recover The thiobarbituric acids are more acidic than
rapidly from anesthesia. Abuse can lead to ad- the barbituric acids. They dissolve in aqueous al-
diction. kali, but the heterocyclic ring opens after a time.
Trade Names. Brevane (Elanco, USA); Brevital They are prepared by condensation of substi-
Sodium (Eli Lilly). tuted malonic esters, malononitrile, malononi-
trile esters, or malonamide esters with thioureas
Hexobarbital [56-29-1], 5-(cyclohexen-1- or N-alkylthioureas, whereby the imino deriva-
yl)-1,5-dimethylbarbituric acid, M r 236.26. The tives initially produced are hydrolyzed to thio-
acid forms colorless crystals that turn pink on ex- barbituric acids [22].
posure to light, mp 146 ◦ C. A 10 % aqueous so-
lution of the sodium salt [50-09-9], M r 258.25, Thiopental sodium [71-73-8], the sodium
has a pH of 11.5. salt of 5-ethyl-5-(1-methylbutyl)thiobarbituric
acid [76-75-5], M r 264.35, a yellowish-white,
crystalline, slightly bitter powder, is very sol-
uble in water and soluble in alcohol. The com-
pound is hygroscopic and has a weak unpleasant
odor. The free acid forms colorless crystals, mp
Hexobarbital sodium is prepared by conden- 158 – 159 ◦ C. A 10 % solution of the sodium salt
sation of methyl(cyclohexen-1-yl)cyanoacetic has a pH of 10.6.
ester with dicyanodiamide to 5-(cyclohexen-
1-yl)-5-methyl-2,6-diimino-3-cyanobarbituric
acid, followed by methylation with dimethyl
sulfate and hydrolysis with 25 % sulfuric acid
[21].
Hexobarbital sodium is an intravenous anes- It is prepared by condensation of thiourea with
thetic for short procedures and combination a disubstituted malonic ester [23].
anesthesia. Hexobarbital is tolerated by tissue Thiopental sodium is a short-acting intra-
much better than thiopental and has proved effi- venous anesthetic used for brief surgical proce-
dures and induction of anesthesia. It is a potent,
8 Anesthetics, General
rapidly effective hypnotic. Sleep ensues within Trade Names. Surital (Parke-Davis); Thiosec-
30 – 60 s. A disadvantage is the lengthy hang- onal (Eli Lilly); Bio-Tal (Philips Roxane, vet-
over. In the United States and Great Britain it is erinary anesthetic).
the most widely used injection anesthetic. Abuse
can lead to addiction. Buthalital sodium [510-90-7], the sodium
Thiopental sodium is used in a mixture with salt of 5-allyl-5-isobutyl-2-thiobarbituric acid,
approximately 6 % sodium carbonate. M r 262.31, is a water-soluble amorphous pow-
Trade Names. Farmotal (Farmitalia); Hypnos- der. The free acid [468-65-5], M r 240.33, melts
tan (Leiras, Turku); Intraval (May & Baker); at 147 ◦ C. Buthalital sodium is prepared by con-
Leopental (Leo); Nesdomal (Specia); Pen- densation of thiourea with a malonic ester [27],
tothal (Abbott); Pentothal-Natrium (Deutsche [28].
Abbott); Thio-Barbityral (Amino, Neuenhof,
Switzerland); Thionembutal (Abbott); Thiobar-
bital (Miro, Palma de Mallorca); Thiopental
“Lentia” (Hormonchemie, Munich); Trapanal
(Promonta; Byk Gulden).
Buthalital sodium is eliminated so rapidly that
Thiobutabarbital sodium [947-08-0], slow injection does not produce anesthesia [29].
the sodium salt of 5-sec-butyl-5-ethyl- For pharmacological properties, see [30].
thiobarbituric acid, M r 241.32, is a yellowish- Trade Names. Baytinal (Bayer); Transithal
white amorphous powder soluble in water and (May & Baker); Ulbreval (Wyeth).
alcohol. The colorless crystals of the free acid
[2095-57-0] melt at 163 – 165 ◦ C. Thiobutabar- Thialbarbital [467-36-7], 5-allyl-5-(cy-
bital is prepared from thiourea and a malonic clohexen-2-yl)-2-thiobarbituric acid, Mr
ester [24]. 264.36, mp 79 – 81 ◦ C. The sodium salt
[3546-29-0], M r 286.34, is a pale yellowish,
water-soluble, amorphous powder.
with HCl-KSCN to yield ethyl 2-mercapto-1-(α- The sodium salt is available as a 24 % aque-
methylbenzyl)-5-imidazolecarboxylate, which ous solution.
is then oxidatively desulfurized [36]. The (R) Trade Names. Somsanit (Kühler Chemie);
isomer is obtained by separating the racemic Gamma-OH (Ebifarm); Anetamin (Sankyo);
acid with (R)-(+)-1-phenylethylamine. Gioron (Kaken-Ono, Japan).
4.2. Benzodiazepines
Among the benzodiazepines, diazepam and flu-
Etomidate is administered intravenously as nitrazepam were used because of their sedative,
a short-acting anesthetic for the induction of anxiolytic, muscle relaxant, and anesthetic po-
lengthy anesthesia, especially for the induction tentiating effects; initially, they were adminis-
of neuroleptanalgesia (Section 4.4) and inhala- tered perorally but later also by injection. The
tion anesthesia [37], [38]. Etomidate produces frequency of pain at the injection site and of
3 – 5 min of sleep. postoperative phlebothromboses led to the de-
Trade Names. Hypnomidate (Janssen; John- velopment of the water-soluble midazolam.
son & Johnson; Sanwakagaku Kankyusho; Ab-
bott) as a 0.2 % solution; Radenarcon Midazolam maleate [59467-70-8], 8-
(Arzneimittelwerk Dresden). chloro-6-(2-fluorophenyl)−1-methyl-4H-
imidazo[1,5-a]-[1,4]benzodiazepine maleate
Sodium oxybate [502-85-2], sodium γ- [59467-94-6], M r 441.59, mp 148 – 151 ◦ C, is a
hydroxybutyrate, HOCH2 CH2 CH2 COONa, M r stable, water-soluble powder. The solubility in
126.09, is recrystallized from alcohol and is sol- water depends on pH: ≈ 85 mg/mL at pH 2.7 and
uble in water. It is prepared by saponification of 0.3 mg/mL at pH 7.6. The free base, M r 325.78,
γ-butyrolactone [39]. melts at 152 – 154 ◦ C. The maleate is subject to
The substance is related to γ-aminobutyric reversible ring opening. Below pH 4 the ring is
acid, a cerebral metabolite that is supposed to open; above pH 4 the cyclic form is present. The
be sleep inducing. When given i.p., it produces anesthetic formulation is a buffered aqueous
a shallow anesthesia (tolerance stage a: paraly- solution containing 2.5 mg/mL at pH 3.5.
sis of the spinal cord and mesencephalon, slight
relaxation of the muscles, see Chap. 1) that
resembles natural sleep as seen via the elec-
troencephalograph. It is employed as an anes-
thetic during labor and in combination anesthe-
sia with nitrous oxide, barbiturates, or neurolep-
tanalgesics.
Anesthetics, General 11
The preparation starts with 7-chloro- narcosis and for induction of lengthy anesthe-
5-(2-fluorophenyl)−1,3-dihydro-2H-1,4- sia. The first commercially available as an anes-
benzodiaze-pinone [41]. For the literature, also thetic was 21-hydroxypregnane-3,20-dione, as
see [42]. the water-soluble sodium hemisuccinate, un-
Midazolam is approximately twice as active der the generic name hydroxidione and by the
as diazepam, causes less pain at the injection trade names Presuren (Schering) and Viadril
site, and has a shorter half-life than diazepam. (Boehringer Mannheim; Pfizer).
Side effects: dose-dependent cerebral depres- The compound has been withdrawn in Great
sion with tranquilization, sedation, and dryness. Britain and other countries, for, even when
Reduction in blood pressure, respiratory depres- strongly diluted, it irritates the venous wall, in-
sion, and cardiovascular effects were slight. creasing the risk of thrombosis, and elicits a
long recovery phase. It is characterized by a
late onset of the anesthesia after a relatively
long, excitation-free induction period of 5 min.
The induction period depends on the hydrolysis
of the hemisuccinate ester to the active steroid
alcohol. Viadril G, in which the hemisuccinate
is combined with glycine, is supposed to be
better tolerated. Most of the disadvantages can
be avoided by dissolving the active pregnane
derivative in Cremophor EL (BASF) [45].
A marked oversensitivity of patients to Al-
thesin [45] led to the development of the
water-soluble steroid minaxolone [44] (Glaxo-
Allenbury), which is still being tested clinically.
mp149 – 151 ◦ C, is soluble in water (1 g per 28th ed., The Pharmaceutical Press, London
40 mL at 20 ◦ C) and methanol. For prepara- 1982, pp. 740 – 761. H. Benzer, R. Frey,
tion → Analgesics and Antipyretics. W. Hügin, O. Mayrhofer: Lehrbuch der
Anaesthesiologie, Reanimation und
Intensivtherapie, Springer Verlag, Berlin
1977. R. Dudziak: Lehrbuch der
Anästhesiologie, F. K. Schattauer Verlag,
Stuttgart – New York 1980. T. C. Gray, J. F.
Nunn, J. E. Utting: General Anaesthesia,
Fentanyl belongs to the group of base- Butterworths, London 1980. C. Nemes, M.
substituted propionanilide analgesics [50] and Niemer, G. Noack: Datenbuch
is a typical morphine agonist. Because of the Anästhesiologie, G. Fischer Verlag, Stuttgart –
danger of addiction, the short-acting fentanyl New York 1979.
is used exclusively for anesthesia. A dose of
just 0.2 – 0.3 mg produces complete short-term Specific References
analgesia in adults. Because it depresses respi- 2. ICI, GB 767779, 1954.
ration, it is necessary to control breathing dur- 3. Hoechst, US 2956624, 1960.
ing neuroleptanalgesia. Afterward, respiratory 4. J. F. Artusio, J. Weingram, Y. J. Sohn, Anesth.
depression can be alleviated by a morphine an- Analg. (Cleveland) 46 (1967) 657. G. W.
tagonist such as 1-N-allyl-3-hydroxymorphinan Black, R. S. Carke, P. J. Howard, H.
(Lorfan). McCullough, Br. J. Anaesth. 41 (1969) 288.
Trade Names. Fentanyl (Janssen, Düsseldorf), 5. Dow Chemical, US 2971990, 1957.
Sublimaze (Janssen); Thalamonal, see trade 6. Merck Sharp & Dohme, US 2021872,1931.
Squibb, US 2136387, 1936.
names for Droperidol.
7. Consortium für elektrochem. Ind.,
US 2832807, 1953.
8. Drugs Future 1 (1976) 307, 7 (1982) 440.
5. References 9. Drugs Future 2 (1977) 153.
10. Drugs Future 5 (1980) 488.
General References 11. Drugs Future 3 (1978) 323.
1. M. E. Greig in V. E. Grill (ed.): Theories of 12. R. C. Terrell, L. Speers et al., J. Med. Chem.
Anaesthesia in Pharmacology and Medicine, 14 (1971) 517.
McGraw-Hill, New York 1954. H. Kilian, H. 13. R. C. Terell, L. Speers et al., J. Med. Chem. 15
Weese: Die Narkose, Thieme Verlag, Stuttgart (1972) 604. Air Reduction Co.,
1954. M. B. Chenoweth (ed.): “Modern DE 1 138 406,1969; US 3 469 011,1969;
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experimentellen Pharmakologie, 14. W. T. Miller, Jr., E. W. Fager, P. H. Griswold, J.
Heffter-Heubner, New Series, vol. XXX, Am. Chem. Soc. 70 (1948) 431. J. D. Park, .
Springer Verlag, Berlin 1972. AMA, Drug C. H. Snow, J. R. Laiker, J. Am. Chem. Soc.
Evaluations by American Medical Assoc., 3rd 73(1951) 861. Dow Chemical, GB 928786,
ed., Publ. Sciences Group, Acton, Mass., 1960.
1977, pp. 285 – 299. J. W. Dundee, W. C. 15. Air Reduction Co., DE 1 814 962, 1969;
McCaughy: “Drugs in Anaesthetic Practice,” US 3 535 388, 1967; US 3535425, 1967.
in G. S. Avery: Drug Treatment, Adv. Press, Hoechst, DE 2344442, 1973.
Sidney 1976, pp. 215 – 248. J. W. Dundee, 16. W. C. Stevens, T. H. Cromwell et al.,
G. M. Wyant: Intravenous Anaesthesia, Anesthesiology 35 (1971) 8 – 53.
Churchill & Livingstone, Edinburgh 1974. 17. Air Reduction Co., US 2830007, 1958.
J. W. Dundee: “New Intravenous 18. Air Reduction Co., US 2870218, 1959.
Anaesthetics”, Br. J. Anaesth. 51 (1979) 19. J. W. Dundee, Br. J. Anaesth. 51 (1979) 641.
641 – 648. K. A. Lehmann: “Narkose – 20. Eli Lilly, US 2872448, 1956.
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Zeit 11 (1982) 18 – 32. B. Helwig, M. Helwig: 24 (2), 294.
Moderne Arzneimittel, 5th ed., Wissenschaftl. 22. D. L. Tabern, E. H. Volwiler, J. Am. Chem.
Verlags GmbH., Stuttgart 1982, pp. 233 – 248. Soc. 57 (1935) 1961. F. S. Crossley, J. Org.
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14 Anesthetics, General