ENPROFYLLINE

Enprofylline acts as a selective and competitive A2B receptor antagonist with the Ki of 7 μM. Enprofylline also acts as a phosphodiesterase inhibitor. Enprofylline can be used for the research of asthma, chronic obstructive pulmonary disease[1][2][3].

Signaling Pathways >> Metabolic Enzyme/Protease >> Phosphodiesterase (PDE)

Research Areas >> Inflammation/Immunology

Signaling Pathways >> GPCR/G Protein >> Adenosine Receptor

A2B receptor:7 μM (Ki)

Enprofylline (300 μM) completely blocks the release of IL-8 by N-ethylcarboxamidoadenosine (NECA)[1]. Enprofylline (10 μM) inhibits NECA (10 μM) induced proliferation in a concentration-dependent manner[2]. Cell Proliferation Assay[2] Cell Line: Human retinal endothelial cells (HRECs) Concentration: 10 μM Incubation Time: 24, 48, 72 hours Result: NECA (10 μM) induced a time-dependent increase in HREC proliferation as measured by cell counts, achieving approximately 80% of the density of cells exposed to normal growth medium for 3 days. Enprofylline (10 μM) completely blocked the proliferative effect of NECA when added concurrently with the analogue.

Enprofylline increases heart rate (HR). Injection of Enprofylline (7.5 and 30 mg/kg) increases HR in male WT mouse from 529±23 to 590±20 and 562±20 after the low and high dose, respectively[3]. A high dose of Enprofylline (30 mg/kg) also decreases temperature compared with saline injection in female (but not in males) WT mice, but a low dose (7.5 mg/kg) has little effect on mouse temperature[3]. Animal Model: A1RKO mice (were cross-bred to C57BL/6 mice for six generations) and A2ARKO mice (were backcrossed to C57BL/6 mice for more than 10 generations)[3] Dosage: 30 mg/kg Administration: Intraperitoneally injected (bolus) at 2-h intervals Result: Increased HR in male WT mouse from 529±23 to 590±20 and 562±20 after the low (7.5 mg/kg) and high dose (30 mg/kg), respectively.

[1]. I Feoktistov, et al. Adenosine A2b receptors evoke interleukin-8 secretion in human mast cells. An enprofylline-sensitive mechanism with implications for asthma. J Clin Invest. 1995 Oct;96(4):1979-86.

[2]. M B Grant, et al. Proliferation, migration, and ERK activation in human retinal endothelial cells through A(2B) adenosine receptor stimulation. Invest Ophthalmol Vis Sci. 2001 Aug;42(9):2068-73.

[3]. Jiang-Ning Yang, et al. Physiological roles of A1 and A2A adenosine receptors in regulating heart rate, body temperature, and locomotion as revealed using knockout mice and caffeine. Am J Physiol Heart Circ Physiol. 2009 Apr;296(4):H1141-9.

MOLECULAR FORMULA :

C8-H10-N4-O2

MOLECULAR WEIGHT :

194.22

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 :

481 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

PLRCAT Pharmacological Research Communications. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1969- Volume(issue)/page/year: 22(Suppl 2),125,1990

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

254 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

PLRCAT Pharmacological Research Communications. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1969- Volume(issue)/page/year: 22(Suppl 2),125,1990

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

157 mg/kg

TOXIC EFFECTS :

Behavioral - altered sleep time (including change in righting reflex)

REFERENCE :

APTOA6 Acta Pharmacologica et Toxicologica. (Copenhagen, Denmark) V.1-59, 1945-86. For publisher information, see PHTOEH Volume(issue)/page/year: 49,313,1981