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| Name(s) |
Structure |
Molecular Formula |
Chemical Abstracts Service Registry Number |
| BZ
a-hydroxy-a-phenylbenzeneacetic acid, 1-azabicyclo[2.2.2]oct-3-yl ester;
3-quinuclidinyl benzilate |
|
C 21H 23NO 3 |
6581-06-2 |
| LSD
9,10-didehydro-N,N-diethyl-6- methyl-8b-ergoline-8-carboxamide
N,N-diethyl lysergamide |
|
C 20H 25N 3O |
50-37-3 |
BZ
BZ has the chemical name a-hydroxy-a-phenylbenzeneacetic acid, 1-azabicyclo[2.2.2]oct-3-yl ester, and has the molecular formula C 21H 23NO 3 and formula weight 337.42. Its Chemical Abstracts Service registry number is 6581-06-2. The melting point of BZ is 164-165ÜC.
BZ was weaponized in bomblets with a pyrotechnic mixture. The pyrotechnic mixture was ignited, and produced a solid aerosol of the high-melting BZ. Production of BZ in the United Sates began in 1962 at Pine Bluff Arsenal and lasted through the late 60s. Between 1988 and 1990, the BZ munitions were destroyed, also at Pine Bluff. No BZ munitions remain in the US stockpile.
There was an unproven allegation that BZ was used in July 1995 on 5,000 Bosnian refugees from Srebrenica. Survivors of the forced march remainder experienced hallucinations leading them to believe they were the victims of chemical weapons. Hay conducted interviews with some of the survivors; his paper provides a review of the literature on BZ as a cause of hallucinations. While CW exposure could not be ruled out, Hay concluded that the hallucinations were the consequence of multiple stresses such as artillery attacks, exhaustion, starvation, thirst and the effects of drinking unpurified water. 1
BZ is an incapacitating agent. Approximately 30 minutes after exposure to a BZ aerosol, symptoms such as disorientation with visual and auditory hallucinations begin to appear. The symptoms peak in four to eight hours, and may take up to four days to pass. Other symptoms can include distended pupils, dry mouth, and increased body temperature.
 The action of BZ on the central and peripheral nervous systems resembles that of atropine. Like atropine, BZ binds to muscarinic acetylcholine receptors. As a result BZ is widely used in research; a search of PubMed on "quinuclidinyl benzilate" produced 2,535 referencesand a recent search of Chemical Abstracts produced 421 references since 1967. Given the extensive body of literature on BZ, it is impractical to provide a thorough review. Several leading references are provided as aid to accessing the literature.
 Binding studies on stereoisomers of 3-quinuclidinyl esters have shown that it is the (R)-stereoisomer that has the greater affinity for the muscarinic acetylcholine receptors. 2 Weapons grade BZ is a mixture of both stereoisomers.
Hydrolysis
Hull, Rosenblatt, and Epstein determined the hydrolysis kinetics of BZ over the pH 0-14 range at different temperatures from 0 to 100ÜC. 3
References
1. Hay, A., Surviving the impossible: the long march from Srebrenica. An investigation of the possible use of chemical warfare agents, Med. Confl. Surviv., 1998, 14(2), 120-155.
2. Rzeszotarski, W. J.; McPherson, D. W.; Ferkany, J. W.; Kinnier, W. J.; Noronha-Blob, L.; Kirkien-Rzeszotarski, A., Affinity and selectivity of the optical isomers of 3-quinuclidinyl benzilate and related muscarinic antagonists, J. Med. Chem., 1988, 31(7), 1463-1466.
3. Hull, L. A.; Rosenblatt, D. H.; Epstein, J., 3-Quinuclidinyl benzilate hydrolysis in dilute aqueous solution, J. Pharm. Sci., 1979, 68(7), 856-859.
Other Leading References
- McDonough, J. H. Jr.; Shih, T. M., A study of the N-methyl-D-aspartate antagonistic properties of anticholinergic drugs, Pharmacol. Biochem. Behav. 1995, 51(2-3), 249-253.
- Rzeszotarski, W. J.; Gibson, R. E.; Eckelman, W. C.; Simms, D. A.; Jagoda, E. M.; Ferreira, N. L.; Reba, R. C., Analogues of 3-quinuclidinyl benzilate, J. Med. Chem., 1982, 25(9), 1103-1106.
- Rauch, B.; Niroomand, F.; Messineo, F. C.; Weis, A.; Kubler, W.; Hasselbach, W., Effect of phospholipid hydrolysis by phospholipase A2 on the kinetics of antagonist binding to cardiac muscarinic receptors, Biochem. Pharmacol. 1994, 48(6), 1289-1296.
- Meyerhoffer, A.; Carlstrom, D, The crystal and molecular structure of quinuclidinyl benzilate hydrobromide, Acta Crystallogr. B, 1969, 25(6), 1119-1126.
LSD
LSD has the chemical name 9,10-didehydro-N,N-diethyl-6- methyl-8b-ergoline-8-carboxamide, and has the molecular formula C 20H 25N 3O and formula weight 323.44. Its Chemical Abstracts Service registry number is 50-37-3. The melting point of LSD is 80-85ÜC.
In 1938, Albert Hofmann and A. Stoll of the Sandoz Research Laboratories first synthesized LSD along with several other derivatives of lysergic acid. However, it was not until April 1943 that the hallucinogenic properties of this substance were accidentally discovered by Hofmann and subsequently confirmed by self-experimentation. During the 1950s, LSD was the subject of considerable interest as a potential chemical warfare agent. In both the US and Britain, test subjects voluntarily ingested LSD in an effort to determine whether LSD could serve as a non-lethal incapacitant. Other tests were done involuntarily; Project MKULTRA tested LSD (along with a large number of other behavior-modifying and psychoactive drugs) on unwitting subjects. At least two fatalities were tied directly to these testing programs; it is probable that more deaths are indirectly related. 1
 The action of LSD on the nervous system results from it being a potent serotonin antagonist. The binding of LSD makes it a useful research tool. In addition, it should be noted that LSD is listed as a Schedule I Controlled Substance (DEA Controlled Substances Code 7315). 2 The potential for abuse of LSD is another reason for the extensive body of research on this substance. By 1966, there were over 300 papers published on LSD; a search of PubMed on "lysergic acid diethylamide” produced 4,741 references and a recent search of Chemical Abstracts produced 1,598 references since 1967. Given the extensive body of literature on LSD, it is impractical to provide a thorough review. Several leading references are provided as aid to accessing the literature.
References
1. Paxman, J.; Harris, R., A Higher Form of Killing : The Secret Story of Chemical and Biological Warfare, Hill and Wang, New York:1982, pp. 187-189, 206-210.
2. 21 CFR 1308.11
Other Leading References
- Pfaff, R. C.; Huang, X.; Marona-Lewicka, D.; Oberlender, R.; Nichols, D. E., Lysergamides revisited, NIDA Res. Monogr., 1994, 146, 52-73.
- Pierce, P. A.; Peroutka, S. J, Antagonist properties of d-LSD at 5-hydroxytryptamine2 receptors, Neuropsychopharmacology, 1990, 3(5-6), 503-508.
- Brown, R. T.; Braden, N. J., Hallucinogens, Pediatr. Clin. North Am., 1987, 34(2), 341-347.
- Heym, J.; Jacobs, B. L ., Serotonergic mechanisms of hallucinogenic drug effects, Monogr. Neural. Sci., 1987, 13, 55-81.
- White, F. J., Comparative effects of LSD and lisuride: clues to specific hallucinogenic drug actions, Pharmacol. Biochem. Behav., 1986, 24(2), 365-379.
- Smith, D. F., Stereochemical considerations of the actions of some psychotropic drugs, Pharmacopsychiatry, 1985, 18(3), 225-230.
- Glennon, R. A.; Rosecrans, J. A., Indolealkylamine and phenalkylamine hallucinogens: a brief overview, Neurosci. Biobehav. Rev., 1982, 6(4), 489-497.
- Vogel, W. H.; Evans, B. D., Structure-activity-relationships of certain hallucinogenic substances based on brain levels, Life Sci., 1977, 20(10), 1629-1635.
- Brimblecombe, R. W., Psychotomimetic drugs: biochemistry and pharmacology, Adv. Drug Res., 1973, 7, 165-206.
- Audio: Ingle, D.; Bushy, R.; Dorman, L.; Brann, E, Iron Butterfly, 1968, Track 6, 14 minutes, 5 seconds to 14 minutes, 25 seconds, backwards.
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