Bromisoval

Bromisoval
	Skeletal formula of bromisoval source ↗
Names
	IUPAC name (RS)-2-Bromo-N-carbamoyl-3-methylbutanamide
Identifiers
CAS Number	496-67-3 Y; 27109-49-5 R Y; 27109-48-4 S Y;
3D model (JSmol)	Interactive image;
ChEBI	CHEBI:31304;
ChEMBL	ChEMBL1515611 Y;
ChemSpider	2353 Y; 129594 R Y; 643139 S Y;
ECHA InfoCard	100.007.115
EC Number	207-825-7;
KEGG	D01391;
MeSH	Bromisovalum
PubChem CID	2447; 146955 R; 735997 S;
UNII	469GW8R486 Y; 3DY4YGA2PX R Y; GTJ4Y0JW4D S Y;
CompTox Dashboard (EPA)	DTXSID2040656 ;
	InChI InChI=1S/C6H11BrN2O2/c1-3(2)4(7)5(10)9-6(8)11/h3-4H,1-2H3,(H3,8,9,10,11) Y Key: CMCCHHWTTBEZNM-UHFFFAOYSA-N Y;
	SMILES CC(C)C(Br)C(=O)NC(N)=O;
Properties
Chemical formula	C6H11BrN2O2
Molar mass	223.070 g·mol−1
log P	1.057
Acidity (pKa)	10.536
Basicity (pKb)	3.461
Pharmacology
ATC code	N05CM03 (WHO)
Routes of; administration	Oral
Related compounds
Related ureas	Carbromal
Related compounds	3-Ureidopropionic acid; beta-Ureidoisobutyric acid; Carbamoyl aspartic acid; N-Acetylaspartic acid; Aceglutamide; N-Acetylglutamic acid; Citrulline;
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Infobox references

Bromisoval (INN), commonly known as bromovalerylurea, is a hypnotic and sedative of the bromoureide group discovered by Knoll in 1907 and patented in 1909.¹ It is marketed over the counter in Asia under various trade names (such as Brovarin²), usually in combination with nonsteroidal anti-inflammatory drugs.

Bromisoval can be prepared by bromination of isovaleric acid by the Hell-Volhard-Zelinsky reaction followed by reaction with urea.

Toxicity

Chronic use of bromisoval has been associated with bromine poisoning.³⁴⁵⁶

Old advertisement for Calmotin. source ↗

It was commonly used in Japan for suicide by overdose. In the 1950s and 1960s, ~4,000 people died each year from bromide poisoning, most commonly from bromvalerylurea.⁷ In Japan, one popular formulation was Calmotin [カルモチン]. Osamu Dazai attempted a double complex suicide with Shimeko Tanabe by overdosing on Calmotin, then drowning at sea. Only Shimeko died. This became the basis for The Flowers of Buffoonery.

The drug was also referred to as the suicide drug in several literature works, including Freezing Point (suicide attempt of the heroine 陽子), The Sea of Fertility (suicide attempt of the heroine's maid, 蓼科).

References

US patent 914518, Saam, E., "Alpha-halogen-isovaleryl-urea and process of making the same", issued 1909-03-09, assigned to Knoll
"Bromisoval". International. Drugs.com.
Hashida, H.; Honda, T.; Morimoto, H.; Aibara, Y. (2001). "市販鎮痛剤常用量の服用による慢性ブロム中毒の1例" [A case of chronic bromvalerylurea intoxication due to habitual use of commercially available nonsteroidal anti-inflammatory drugs presenting an indefinite hyperchloremia] (pdf). Nihon Ronen Igakkai Zasshi. Japanese Journal of Geriatrics (in Japanese). 38 (5): 700–703. doi:10.3143/geriatrics.38.700. ISSN 0300-9173. PMID 11605223.
Kawakami, T.; Takiyama, Y.; Yanaka, I.; Taguchi, T.; Tanaka, Y.; Nishizawa, M.; Nakano, I. (1998). "Chronic bromvalerylurea intoxication: Dystonic posture and cerebellar ataxia due to nonsteroidal anti-inflammatory drug abuse" (pdf). Internal Medicine. 37 (9). Tokyo, Japan: 788–791. doi:10.2169/internalmedicine.37.788. PMID 9804091.
Wang, Y. -T.; Yang, S. Y.; Wu, V. C.; Wu, K. D.; Fang, C. C. (2005). "Pseudohyperchloraemia due to bromvalerylurea abuse". Nephrology Dialysis Transplantation. 20 (8): 1767–1768. doi:10.1093/ndt/gfh945. PMID 15972320.
Arai, A.; Sato, M.; Hozumi, I.; Matsubara, N.; Tanaka, K.; Soma, Y.; Adachi, T.; Tsuji, S. (1997). "Cerebellar Ataxia and Peripheral Neuropathy due to Chronic Bromvalerylurea Poisoning" (pdf). Internal Medicine. 36 (10). Tokyo, Japan: 742–746. doi:10.2169/internalmedicine.36.742. PMID 9372340.
Shimazu, Takeshi (2006). "Do X-ray and CT help diagnose acute poisoning?". Nihon Shuchu Chiryo Igakukai zasshi. 13 (2): 102–105. doi:10.3918/jsicm.13.102. ISSN 1340-7988.

[1] US patent 914518, Saam, E., "Alpha-halogen-isovaleryl-urea and process of making the same", issued 1909-03-09, assigned to Knoll

[2] "Bromisoval". International. Drugs.com.

[3] Hashida, H.; Honda, T.; Morimoto, H.; Aibara, Y. (2001). "市販鎮痛剤常用量の服用による慢性ブロム中毒の1例" [A case of chronic bromvalerylurea intoxication due to habitual use of commercially available nonsteroidal anti-inflammatory drugs presenting an indefinite hyperchloremia] (pdf). Nihon Ronen Igakkai Zasshi. Japanese Journal of Geriatrics (in Japanese). 38 (5): 700–703. doi:10.3143/geriatrics.38.700. ISSN 0300-9173. PMID 11605223.

[4] Kawakami, T.; Takiyama, Y.; Yanaka, I.; Taguchi, T.; Tanaka, Y.; Nishizawa, M.; Nakano, I. (1998). "Chronic bromvalerylurea intoxication: Dystonic posture and cerebellar ataxia due to nonsteroidal anti-inflammatory drug abuse" (pdf). Internal Medicine. 37 (9). Tokyo, Japan: 788–791. doi:10.2169/internalmedicine.37.788. PMID 9804091.

[5] Wang, Y. -T.; Yang, S. Y.; Wu, V. C.; Wu, K. D.; Fang, C. C. (2005). "Pseudohyperchloraemia due to bromvalerylurea abuse". Nephrology Dialysis Transplantation. 20 (8): 1767–1768. doi:10.1093/ndt/gfh945. PMID 15972320.

[6] Arai, A.; Sato, M.; Hozumi, I.; Matsubara, N.; Tanaka, K.; Soma, Y.; Adachi, T.; Tsuji, S. (1997). "Cerebellar Ataxia and Peripheral Neuropathy due to Chronic Bromvalerylurea Poisoning" (pdf). Internal Medicine. 36 (10). Tokyo, Japan: 742–746. doi:10.2169/internalmedicine.36.742. PMID 9372340.

[7] Shimazu, Takeshi (2006). "Do X-ray and CT help diagnose acute poisoning?". Nihon Shuchu Chiryo Igakukai zasshi. 13 (2): 102–105. doi:10.3918/jsicm.13.102. ISSN 1340-7988.

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Toxicity

See also

References