Aminophylline

Aminophylline is a competitive phosphodiesterase 3/4 (PDE3/4) inhibitor. Aminophylline also acts as an adenosine receptor antagonist. Aminophylline elevates intracellular cAMP levels via competitive inhibition of PDE3 and PDE4, antagonizes adenosine A1 receptor (ADORA1), regulates intracellular calcium signaling and synaptic vesicle cycling, upregulates the PPAR signaling pathway, and downregulates glutamatergic synaptic pathways simultaneously. Aminophylline can be used in research related to major depressive disorder, epilepsy, asthma, and chronic obstructive pulmonary disease (COPD)^{[1][2][3][4][5][6]}. In Vitro:Aminophylline Dihydrate binds to PDE3, PDE4, ADORA1, and SERT with varying affinities, showing the strongest binding to PDE4 and weakest binding to ADORA1^[1]. In Vivo:Aminophylline (5-20 mg/kg; i.p.; once daily for 15 consecutive days) Dihydrate exerts dose-dependent antidepressant activity in mice with chronic restraint stress-induced depressive-like behaviors. It significantly reduces the immobility time of mice in the tail suspension test and forced swimming test, and increases their grooming time in the sucrose splash test^[1].
Aminophylline (50-100 mg/kg; i.p.; single administration; treatment 30 min prior to electroshock test) Dihydrate potently reduces the anti-electroconvulsive efficacy of most tested antiepileptic drugs in mice^[2].
Aminophylline (7 mg/kg loading dose + 1.5 mg/kg/hr maintenance dose; i.v.; single continuous infusion; duration ≥ 1.5 h) Dihydrate increases minute ventilation, tidal volume, respiratory rate, parasternal muscle shortening, minute integrated electromyographic activity of the parasternal muscle, and parasternal muscle contractility in awake healthy dogs, while it does not alter tidal electromyographic activity and baseline muscle length of the parasternal muscle^[6].