On the other hand, the agents that block α1 and α2-adrenergic receptors (selectively or not) belong to the sympatholytics (adrenolytics), i.e., agents inhibiting the sympathetic nervous system: imidazoline derivatives (phentolamine,

tolazoline) block both types of α receptors, derivatives of piperazinchinazolin (prazosin, doxazosin, terazosin) block selectively α1 receptors, ergot alkaloids block predominantly α2 receptors, and yohimbine blocks selectively α2 receptors. Blocking agents of α-adrenergic receptors are most commonly used as cardiovascular drugs: α1-blockers as antihypertensive drugs, α2-blockers as hypertensive ones; ergot alkaloids have a contractive effect on the uterus, Protein Tyrosine Kinase inhibitor but their hydrogenated derivatives are devoid of this activity, improving peripheral blood. Non-specific α-blockers accelerate the heart rate, dilate peripheral vessels, increasing MLN2238 order the contractility of intestines and secretory activity of gastric mucosal (Schmitz et al., 1981; Robinson and Hudson, 1998; Fitzpatrick et al., 2004). Over time, agonists and antagonists of adrenoceptors have become the subject of a number of works in the field of molecular modeling, lipophilicity, and structure–activity as well as 3D QSAR (Eric et al., 2004; Balogh et al., 2007, 2009; Nikolic et al., 2008; Zhao et al., 2011; Yadav et al., 2013). Timmermans and co-workers have published interesting series of papers about agonists and antagonists

of adrenoceptors in order to characterization

and classification of selected molecules (Timmermans et al., 1981, 1984; Timmermans and Van Zwieten, 1982). In one of these papers (Timmermans et al., 1984), the authors have considered hypotensive and hypertensive activity relationships of α-adrenomimetics and experimentally determined logarithm of the n-octanol/water partition coefficient, log P, and also experimentally determined binding others affinity to α1 and α2 receptors. Obtained by the authors, relationships according to the activity and logarithm of the partition coefficient were unsatisfactory. More preferably shown themselves to be the relationships in term of binding affinity (R > 0.9). For α-adrenolytics, authors presented relationships according to indexes of α1/α2 adrenoceptor antagonist selectivity in vivo and indexes of α1/α2 adrenoceptor antagonist of pre and postsynaptic selectivity in vivo considering selectivity indexes of binding of α1/α2 adrenoreceptor to the corresponding ones (R > 0.9). The objective of the presented study was to analyze the biological activity data (Timmermans et al., 1984), the parameters of binding affinity to the α1 and α2 receptors together with parameters of the logarithm of the partition coefficient n-octanol/water (log P) using Momelotinib price semi-empirical calculations methods (Bączek, 2006; Bodzioch et al., 2010) for isolated molecules (in vacuo) and the for the molecules placed in an aqueous environment.