droxidopa

Names

[ Name ]:
droxidopa

[Synonym ]:
(-)-(2s,3r)-2-amino-3-hydroxy-3-(3,4-dihydroxyphenyl)propionic acid
DL-DOPS
DL-threo-Dihydroxyphenylserine
L-DOPS
3-dihydroxy-betthreo-dl-tyrosin
(2S,3R)-3-(3,4-Dihydroxyphenyl)-2-amino-3-hydroxypropanoic acid
3-dihydroxy-dl-tyrosinethreo-bet
DROXIDOPA
(2S,3R)-2-Amino-3-(3,4-dihydroxyphenyl)-3-hydroxypropionic Acid
Benzeneethanaminium, α-carboxy-β,3,4-trihydroxy-, inner salt, (αS,βS)-
(2S,3R)-2-Amino-3-(3,4-dihydroxyphenyl)-3-hydroxypropanoic acid
L-threo-DOPS
DL-THREO-DOPS
L-threo-3,4-Dihydroxyphenylserine
(2S,3S)-2-Ammonio-3-(3,4-dihydroxyphenyl)-3-hydroxypropanoate
Droxidopa L-threo 3,4-Dihydroxyphenylserine
DL-threo-Droxidopa
threo-Dopaserine
L-threo-3-(3,4-Dihydroxyphenyl)serine

Biological Activity

[Description]:

Droxidopa(L-DOPS, SM5688) is a synthetic amino acid precursor which acts as a prodrug to the neurotransmitters norepinephrine (noradrenaline) and epinephrine (adrenaline); capable of crossing the protective blood–brain barrierIC50 value: Target: The acute administration of droxidopa in PVL and BDL rats caused a significant and maintained increase in arterial pressure and mesenteric arterial resistance, with a significant decrease of mesenteric arterial and portal blood flow, without changing portal pressure and renal blood flow [1]. L-threo-dihydroxyphenyslerine (Droxidopa) is a pro-drug which has a structure similar to noradrenaline, but with a carboxyl group. It has no pressor effects in this form. It can be administered orally, unlike noradrenaline, and after absorption is converted by the enzyme dopa decarboxylase into noradrenaline thus increasing levels of the neurotransmitter which is identical to endogenous noradrenaline [2].

[Related Catalog]:

Signaling Pathways >> Others >> Others

Natural Products >> Phenylpropanoids

Research Areas >> Neurological Disease

[References]

[1]. Coll M, et al. Droxidopa, an oral norepinephrine precursor, improves hemodynamic and renal alterations of portal hypertensive rats. Hepatology. 2012 Nov;56(5):1849-60.

[2]. Mathias CJ. L-dihydroxyphenylserine (Droxidopa) in the treatment of orthostatic hypotension: the European experience. Clin Auton Res. 2008 Mar;18 Suppl 1:25-9.

[Related Small Molecules]

Chemical & Physical Properties

[ Density]:
1.608g/cm3

[ Boiling Point ]:
549.8±50.0 °C at 760 mmHg

[ Melting Point ]:
232-235° (dec); mp 229-232° (dec) (Ohashi)

[ Molecular Formula ]:
C₉H₁₁NO₅

[ Molecular Weight ]:
213.187

[ Flash Point ]:
286.3±30.1 °C

[ Exact Mass ]:
213.063721

[ PSA ]:
124.01000

[ LogP ]:
-0.95

[ Vapour Pressure ]:
0.0±1.6 mmHg at 25°C

[ Index of Refraction ]:
1.692

[ Storage condition ]:
2-8C

MSDS

Click to get detail MSDS

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: VT9626010

CHEMICAL NAME :: Serine, 3-(3,4-dihydroxyphenyl)-, L-threo-

CAS REGISTRY NUMBER :: 23651-95-8

LAST UPDATED :: 199603

DATA ITEMS CITED :: 12

MOLECULAR FORMULA :: C9-H11-N-O5

MOLECULAR WEIGHT :: 213.21

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: >10 gm/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: -,758,1990

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 84 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: -,758,1990

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 16 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Behavioral - ataxia Lungs, Thorax, or Respiration - other changes

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 15(Suppl 2),257,1987

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: >10 gm/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: -,758,1990

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: >10 gm/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: -,758,1990

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: >100 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: -,758,1990

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: >5 gm/kg

TOXIC EFFECTS :: Cardiac - other changes Lungs, Thorax, or Respiration - dyspnea Kidney, Ureter, Bladder - other changes

REFERENCE :: YKYUA6 Yakkyoku. Pharmacy. (Nanzando, 4-1-11, Yushima, Bunkyo-ku, Tokyo, Japan) V.1- 1950- Volume(issue)/page/year: 40,1935,1989

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Primate - monkey

DOSE/DURATION :: >5 gm/kg

TOXIC EFFECTS :: Cardiac - other changes Lungs, Thorax, or Respiration - respiratory depression Kidney, Ureter, Bladder - other changes

REFERENCE :: YKYUA6 Yakkyoku. Pharmacy. (Nanzando, 4-1-11, Yushima, Bunkyo-ku, Tokyo, Japan) V.1- 1950- Volume(issue)/page/year: 40,1935,1989 ** REPRODUCTIVE DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 13200 mg/kg

SEX/DURATION :: female 15 day(s) pre-mating female 1-7 day(s) after conception

TOXIC EFFECTS :: Reproductive - Maternal Effects - ovaries, fallopian tubes

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 15(Suppl 2),283,1987

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 2200 mg/kg

SEX/DURATION :: female 7-17 day(s) after conception

TOXIC EFFECTS :: Reproductive - Maternal Effects - other effects Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Specific Developmental Abnormalities - musculoskeletal system

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 15(Suppl 2),283,1987

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 1500 mg/kg

SEX/DURATION :: female 17-21 day(s) after conception lactating female 20 day(s) post-birth

TOXIC EFFECTS :: Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain) Reproductive - Effects on Newborn - physical Reproductive - Effects on Newborn - other postnatal measures or effects

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 15(Suppl 2),283,1987

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 15 gm/kg

SEX/DURATION :: female 17-21 day(s) after conception lactating female 20 day(s) post-birth

TOXIC EFFECTS :: Reproductive - Maternal Effects - parturition

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 15(Suppl 2),283,1987

Safety Information

[ Symbol ]:

GHS07

[ Signal Word ]:
Warning

[ Hazard Statements ]:
H315-H319-H335

[ Precautionary Statements ]:
P261-P305 + P351 + P338

[ Hazard Codes ]:
Xi

[ Risk Phrases ]:
36/37/38

[ Safety Phrases ]:
26

[ RIDADR ]:
NONH for all modes of transport

[ RTECS ]:
VT9626010

[ HS Code ]:
29225090

Articles

Application of the BCS biowaiver approach to assessing bioequivalence of orally disintegrating tablets with immediate release formulations.

Eur. J. Pharm. Sci. 64 , 37-43, (2014)

The aim of this study was to compare the dissolution profiles of oral disintegrating tablets (ODTs) and immediate release (IR) formulations in order to experimentally validate the regulatory biowaiver...

[Acute poisoning of droxidopa: report of a case].

Chudoku. Kenkyu. 26(3) , 244-5, (2013)

The noradrenaline precursor L-DOPS reduces pathology in a mouse model of Alzheimer's disease.

Neurobiol. Aging 33(8) , 1651-63, (2012)

Damage to noradrenergic neurons in the locus coeruleus (LC) is a hallmark of Alzheimer's disease (AD) and may contribute to disease progression. In 5xFAD transgenic mice, which accumulate amyloid burd...