Description
3-Propylxanthine is a xanthine derivative that antagonizes adenosine receptors (K
is = 44, 32, and 6.3 μM for A
1, A
2A, and A
2B, respectively) and cAMP phosphodiesterase (K
i = 42 μM). Through these actions, 3-propylxanthine induces smooth muscle relaxation, blocks smooth muscle contraction and VEGF secretion driven by adenosine receptor agonists, and reduces bronchial hyperresponsiveness.
Uses
Enprofylline is a xanthine lacking adenosine receptor antagonism.
Definition
ChEBI: Xanthine bearing a propyl substituent at position 3. A bronchodilator, it is used for the symptomatic treatment of asthma and chronic obstructive pulmonary disease, and in the management of cerebrovascular insufficiency, sickle cell disease, and diabetic n
uropathy.
in vivo
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. |
IC 50
A2B receptor: 7 μM (Ki)
References
[1] J LINDEN. Characterization of human A(2B) adenosine receptors: radioligand binding, western blotting, and coupling to G(q) in human embryonic kidney 293 cells and HMC-1 mast cells.[J]. Molecular Pharmacology, 1999, 56 4: 705-713.
[2] K. OGAWA T. S K Takagi. Mechanism of xanthine-induced relaxation of guinea-pig isolated trachealis muscle[J]. British Journal of Pharmacology, 1989, 97 2: 542-546. DOI:
10.1111/j.1476-5381.1989.tb11983.x[3] U SCHWABE M J L D Ukena. Xanthine derivatives as antagonists at A1 and A2 adenosine receptors.[J]. Naunyn-Schmiedeberg’s archives of pharmacology, 1985, 330 3: 212-221. DOI:
10.1007/bf00572436[4] BIRGITTE HIER. Contraction-induced secretion of VEGF from skeletal muscle cells is mediated by adenosine.[J]. American journal of physiology. Heart and circulatory physiology, 2010: H857-62. DOI:
10.1152/ajpheart.00082.2010[5] G H KOTER. Effect of theophylline and enprofylline on bronchial hyperresponsiveness.[J]. Thorax, 1989, 44 12: 1022-1026. DOI:
10.1136/thx.44.12.1022
