Dipivefrin HCl

Names

[ Name ]:
Dipivefrin HCl

[Synonym ]:
Dipivefrin HCL
EINECS 264-609-5
AKPro
Dipivefrin hydrochloride
[2-(2,2-dimethylpropanoyloxy)-4-[1-hydroxy-2-(methylamino)ethyl]phenyl] 2,2-dimethylpropanoate,hydrochloride
(1)-4-(1-Hydroxy-2-(methylamino)ethyl)-1,2-phenylene dipivalate hydrochloride
Dipivalyl epinephrine hydrochloride
Dipivefrine hydrochloride

Biological Activity

[Description]:

Dipivefrin hydrochloride (Dipivefrine hydrochloride) is an antiglaucoma prodrug that is hydrolyzed to the active compound, epinephrine, by esterases in the cornea[1][2].

[Related Catalog]:

Signaling Pathways >> Others >> Others

Research Areas >> Neurological Disease

[In Vivo]

Dipivefrin hydrochloride (0.3-10 μg/kg; i.p.;) induces enhancement of memory involves central beta- but not alpha-adrenergic mechanisms[3]. Animal Model: Male 60-day-old CFW mice (23-28 g)[3] Dosage: 0.3 μg/kg, 1.0 μg/kg, 3.0 μg/kg, 10 μg/kg Administration: Intraperitoneal injection; post-training Result: Significantly enhanced retention of both inhibitory avoidance and Y-maze discrimination tasks in a dose-dependent manner.

[References]

[1]. Edgar DF, et al. Effects of dipivefrin and pilocarpine on pupil diameter, automated perimetry and LogMAR acuity. Graefes Arch Clin Exp Ophthalmol. 1999 Feb;237(2):117-24.

[2]. Anderson JA, et al. Effects of echothiophate on enzymatic hydrolysis of dipivefrin. Arch Ophthalmol. 1984 Jun;102(6):913-6.

[3]. Introini-Collison I, et al. Memory-enhancing effects of post-training dipivefrin and epinephrine: involvement of peripheral and central adrenergic receptors. Brain Res. 1992 Feb 14;572(1-2):81-6.

Chemical & Physical Properties

[ Boiling Point ]:
473.7ºC at 760 mmHg

[ Melting Point ]:
158-159°

[ Molecular Formula ]:
C₁₉H₃₀ClNO₅

[ Molecular Weight ]:
387.89800

[ Flash Point ]:
240.3ºC

[ Exact Mass ]:
387.18100

[ PSA ]:
84.86000

[ LogP ]:
4.03530

[ Water Solubility ]:
Freely soluble in water, very soluble in methanol, freely soluble in ethanol (96 per cent) and in methylene chloride.

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: UA2459550

CHEMICAL NAME :: Propanoic acid, 2,2-dimethyl-, 4-(1-hydroxy-2-(methylamino)ethyl)-1,2-phenylene ester, hydrochloride, (+-)-

CAS REGISTRY NUMBER :: 64019-93-8

LAST UPDATED :: 199212

DATA ITEMS CITED :: 11

MOLECULAR FORMULA :: C19-H29-N-O5.Cl-H

MOLECULAR WEIGHT :: 387.95

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 :: 183 mg/kg

TOXIC EFFECTS :: Sense Organs and Special Senses (Eye) - mydriasis (pupillary dilation) Behavioral - convulsions or effect on seizure threshold Behavioral - ataxia

REFERENCE :: KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 20,25,1986

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

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 8500 ug/kg

TOXIC EFFECTS :: Sense Organs and Special Senses (Eye) - mydriasis (pupillary dilation) Behavioral - convulsions or effect on seizure threshold Behavioral - ataxia

REFERENCE :: KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 20,25,1986

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

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 21200 ug/kg

TOXIC EFFECTS :: Sense Organs and Special Senses (Eye) - mydriasis (pupillary dilation) Behavioral - convulsions or effect on seizure threshold Behavioral - ataxia

REFERENCE :: KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 20,25,1986

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 224 mg/kg

TOXIC EFFECTS :: Behavioral - altered sleep time (including change in righting reflex) Behavioral - somnolence (general depressed activity) Lungs, Thorax, or Respiration - dyspnea

REFERENCE :: KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 20,25,1986

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

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 32700 ug/kg

TOXIC EFFECTS :: Behavioral - altered sleep time (including change in righting reflex) Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - dyspnea

REFERENCE :: KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 20,25,1986

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

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 35 mg/kg

TOXIC EFFECTS :: Behavioral - altered sleep time (including change in righting reflex) Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - dyspnea

REFERENCE :: KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 20,25,1986

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

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 4 mg/kg

TOXIC EFFECTS :: Behavioral - convulsions or effect on seizure threshold Behavioral - ataxia Lungs, Thorax, or Respiration - dyspnea

REFERENCE :: KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 20,25,1986 ** OTHER MULTIPLE DOSE TOXICITY DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 260 mg/kg/30D-I

TOXIC EFFECTS :: Endocrine - other changes Blood - changes in spleen Nutritional and Gross Metabolic - weight loss or decreased weight gain

REFERENCE :: KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 20,75,1986

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 780 mg/kg/13W-I

TOXIC EFFECTS :: Cardiac - other changes Endocrine - other changes Nutritional and Gross Metabolic - weight loss or decreased weight gain

REFERENCE :: KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 20,75,1986 ** REPRODUCTIVE DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Subcutaneous

DOSE :: 18900 ug/kg

SEX/DURATION :: male 4 week(s) pre-mating

TOXIC EFFECTS :: Reproductive - Paternal Effects - testes, epididymis, sperm duct

REFERENCE :: KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 20,25,1986

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Subcutaneous

DOSE :: 13500 ug/kg

SEX/DURATION :: female 17-22 day(s) after conception lactating female 21 day(s) post-birth

TOXIC EFFECTS :: Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain)

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 31,1083,1986

Safety Information

[ RIDADR ]:
UN 2811 6.1 / PGIII

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