The pharmacodynamic profile of a new
xanthine derivative, 7-[(2,2-dimethyl)propyl]-1-methyl
xanthine (CAS 155006-67-0, MX2/120), was investigated in comparison with
theophylline. The compound reduces in vitro the bronchospastic tone induced by
carbachol or
histamine in guinea-pig bronchi, with a potency 11 and 5 fold greater than
theophylline, respectively. MX2/120 is significantly more active and long-lasting than
theophylline in in vivo experiments toward spasmogens such as
acetylcholine (ED50 over 5 h = 15 mumol/kg p.o. vs 230 mumol/kg p.o.) or
histamine (ED50 over 5 h = 122 mumol/kg p.o. vs 500 mumol/kg p.o.) while being almost equiactive to
theophylline toward
antigen and
capsaicin induced
cough strokes. MX2/120, if administered by i.p. route reduces hyperresponsiveness to
histamine induced by PAF and extravasation of
protein into bronchoalveolar lavage fluid induced by
capsaicin. These anti-inflammatory effects of MX2/120 are of similar extent when compared to
theophylline. Unlike
theophylline, MX2/120 up to 275 mumol/kg p.o. possesses little or no CNS excitatory effects in mice in terms of reduction of sleeping time induced by
chlordiazepoxide, increase in mortality and convulsions induced by pentetrazol and increase in locomotor activity. This reduced neuroexcitatory action is probably related to its lack of affinity to
adenosine receptors that could also explain the absence of effect on basal gastric secretion. Chronotropic effects of MX2/120 in conscious rats are similar to those of
theophylline while the effects of both drugs on blood pressure are of minor extent. The overall pharmacodynamic properties of MX2/120 are superior to those of
theophylline in relation to its antibronchospastic activity and lack of excitatory effects on CNS.