aminophylline brands

Molecular formula: C16H24N10O4

Aminophylline is the ethylenediamine salt of theophylline. After ingestion, theophylline is released from aminophylline, and theophylline relaxes the smooth muscle of the bronchial airways and pulmonary blood vessels and reduces airway responsiveness to histamine, methacholine, adenosine, and allergen. Theophylline competitively inhibits type III and type IV phosphodiesterase (PDE), the enzyme responsible for breaking down cyclic AMP in smooth muscle cells, possibly resulting in bronchodilation. Theophylline also binds to the adenosine A2B receptor and blocks adenosine mediated bronchoconstriction. In inflammatory states, theophylline activates histone deacetylase to prevent transcription of inflammatory genes that require the acetylation of histones for transcription to begin. Theophylline and aminophylline have been widely used as inhibitors of phosphodiesterase when examining the role of cAMP in regulating cell function. In reality, however, these phosphodiesterase inhibitors may have additional sites of action that could complicate the interpretation of the results. These additional sites of action could include antagonism of inhibitory adenosine autoreceptors and release of intracellular calcium. The purpose of the present study was to determine which of the above three is the primary mechanism by which theophylline and aminophylline affect transmitter release at the mammalian neuromuscular junction. Quantal release measurements were made using intracellular recording techniques. A variety of drugs were used to elucidate this pathway. Isoproterenol, an adenylate cyclase activator, was first used to establish the effect of enhanced levels of cAMP. Theophylline application on its own or in the presence of a drug combination that blocked the adenosine receptor and phosphodiesterase pathways caused significant release depression, opposite to what is expected if it was functioning to enhance cAMP levels. However, when applied in the presence of a drug combination that blocked the adenosine receptor, phosphodiesterase and intracellular ryanodine calcium pathways, theophylline was unable to depress release. Therefore, it was concluded that the major mechanism of action of theophylline is depression of transmitter release by causing the release of intracellular calcium. Aminophylline application alone resulted in a significant enhancement of release. However, when coupled with an adenosine receptor blocker, the ability of aminophylline to enhance transmitter release was blocked, suggesting that its dominant mechanism of action is adenosine receptor inhibition. Taken together, these results indicate that the use of theophylline and aminophylline is inappropriate when examining the role of cAMP at the mammalian neuromuscular junction. Theophylline has two distinct actions in the airways of patients with reversible obstruction; smooth muscle relaxation (i.e., bronchodilation) and suppression of the response of the airways to stimuli (i.e., non-bronchodilator prophylactic effects). While the mechanisms of action of theophylline are not known with certainty, studies in animals suggest that bronchodilatation is mediated by the inhibition of two isozymes of phosphodiesterase (PDE III and, to a lesser extent, PDE IV) while non-bronchodilator prophylactic actions are probably mediated through one or more different molecular mechanisms, that do not involve inhibition of PDE III or antagonism of adenosine receptors. Some of the adverse effects associated with theophylline appear to be mediated by inhibition of PDE III (e.g., hypotension, tachycardia, headache, and emesis) and adenosine receptor antagonism (e.g., alterations in cerebral blood flow). Theophylline increases the force of contraction of diaphragmatic muscles. This action appears to be due to enhancement of calcium uptake through an adenosine-mediated channel. /Theophylline/

Source: PubChem (NCBI) · compound 9433