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Bruger, M.,and Silberbush, F, F., J. Clin. Endocrin. 6: 565, 1946. 
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Reineke, E. P., and Turner, C. W. J. Dairy Sci. 27: 793, 1944. 
Robertson, J, D. J. Endocrin. 4: 300, 1945. 
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Roche, Jean, Michel, R., and Volpert, E. Compt. Rend. Soc. Biol. 150: 2149, 1956, 
oawnonnrteanun kh WN & 
TRANQUILIZERS IN ANIMALS 
During the last few years, a massive volume of literature has materialized on the 
therapeutic use of the tranquilizing agents. More recently, the value of these agents in 
animal nutrition has been tested, and a respectable volume of literature has already 
appeared in this limited field alone. In addition to Rauwolfia vomitoria and reserpine, 
the drugs tested in animal nutrition studies include: Chlorpromazine, hydroxyzine, per- 
phenazine, prochlorperazine, tetrahydrozoline, trifluoperozine, and others. 
In constrast with the massive existing literature on therapeutic and nutritional uses 
of the tranquilizers almost nothing has been published on tissue accumulation and meta- 
bolic fate of the drugs. An example of the paucity of information on the subject is given 
by the National Research Council Handbook (on) Tranquilizers (1), published early in 
1959. While information on 26 tranquilizing drugs is given by the handbook, metabolic 
information is given on only three, as follows: (1) ‘‘Chlorpromazine is known to be 
converted, in part, to the sulfoxide, but the major metabolites are still unknown.” 
(2) ‘‘Iproniazidis rapidly split into isopropyl hydrazine (the active moiety) and isonicotinic 
acid, the latter being promptly excreted in the urine. The long duration of action of 
iproniazid as an amine oxidase inhibitor may be accounted for by the attachment of the 
isopropyl hydrazine moiety to the amine oxidase.’’ (3) Meprobamate ‘‘A portion of the 
drug is found inurine as a conjugate with glucuronic acid, and 10% is recovered unreacted. 
The major metabolites of meprobamate are unknown.’’ During the year that has elapsed 
since the publication of the handbook, relatively little additional information has been 
published on this subject. 
Excretion 
Such information as has been published on the metabolism of the tranquilizers seems 
to be, to some extent, mutually contradictory. An early contribution to knowledge of the 
rate of excretion of chlorpromozine from the body was made by Dubost and Pascal in 
1953 (2). These workers reported that following oral doses ranging from 0.25 to 0.5 gm. 
per kg. of bodyweight, the blood level of the drug in man is 4 to 8 mg. per liter after 
3 hours, dropping to 2.4 to 4 mg. per liter after 6 hours, and to 1.7 to 2.5 mg. per liter 
after 24 hours. Only 7 to 8 percent of the ingested drug appears in the urine. Given 
subcutaneously in doses of 0.1 to 0.25 gm. per kg., the blood concentration of chlor- 
promazine falls more rapidly than it does when administered by mouth. Reports vary 
as to the percentage of chlorpromazine excreted through the kidney. Berti, et al. (3) 
reported that in the rat, guinea pig, rabbit, and man 20 percent of the dose leaves the 
body in 4 days while the percentage eliminated in this way by the dog is twice that of the 
other species studied. The excretion rate appeared to be independent of level of dosage 
219 
