Adrenoreceptor antagonists

Similar to dihydropyridine calcium blockers, many 0-adrenoreceptor antagonists exhibit antioxidant activity. Mak and Weglinski [290] showed that the pretreatment of canine myocytic sarcolemmal membranes with 0-adrenoreceptor antagonists (propranolol, pindolol, metoprolol, atenolol, or sotalol) (Figure 29.15) inhibited superoxide-induced sarcolemmal... 

Rosini, M., Bolognesi, M.L., Giardina, D., Minarini, A., Tumiatti, V. and Melchiorre, C. (2007) Recent advances in alphal-adrenoreceptor antagonists as pharmacological tools and therapeutic agents. Current Topics in Medicinal Chemistry, 7, 147-162. 

The [ -adrenoreceptors antagonists (also called [)-blockers) comprise a group of chiral drugs that are mostly used in the treatment of cardiovascular disorders such as hypertension, cardiac arrhythmia, or ischemic heart disease. Teicoplanin is the chiral selector most exploited for the enantioseparation of this class of compounds, followed by vancomycin. Several P-blockers have been analyzed, particularly in the... 

When using PFT with a neutral selector, it is quite difficult to avoid any entrance of the chiral selector into the ionization source, particularly at a high pH, where EOF is important. The use of BGE at low pH and/or coated capillary to minimize EOF is therefore mandatory. However, the coaxial sheath gas, which generally assists the ionization process, leads to an aspirating phenomenon of the chiral selector in the MS direction. Javerfalk et al. were the first to apply PFT with a neutral methyl-/i-CD for the separation of racemic bupivacaine and ropivacaine with a polyacrylamide-coated capillary and an acidic pH buffer (pH 3). Cherkaoui et al. employed another neutral CD (HP-/1-CD) with a PVA-coated capillary for the analysis of amphetamines and their derivatives. To prevent a detrimental aspiration effect, analyses were carried out without nebulization pressure. Numerous other studies presented excellent results such as the enantioselective separation of adrenoreceptor antagonist drugs using tandem mass spectrometry (MS/MS) the separation of clenbuterol enantiomers after solid-phase extraction (SPE) of plasma samples or the use of CD dual system for the simultaneous chiral determination of amphetamine, methamphetamine, dimethamphetamine, and p-hydroxymethamphetamine in urine. 

Grard, S., Morin, P., Dreux, M., and Ribet, J. P. (2001). Efficient applications of capillary electrophoresis-tandem mass spectrometry to the analysis of adrenoreceptor antagonist enantiomers using a partial filling technique. /. Chromatogr. A 926, 3 — 10. 

The mechanism of action of these drugs is not completely understood. However, it is very likely that they inhibit cellular phosphodiesterase of the myocardium, which leads to an elevation in the cellular level of cyclic AMP, which in turn facihtates contraction of myocardial cells. It is clear that these drags are not 8-adrenoreceptor antagonists, and that their effect is not mediated by inhibition of (Na -K+) ATPase. They simultaneously increase the flow of calcium ions into the cell. They are used for short-term control of patients that inadequately react to cardiac glycosides, diuretics, and coronary vasodilating agents. 

Lader, M. (1988) Beta-adrenoreceptor antagonists in neuropsychiatry an update. / Clin Psychiatry 49 213—223. 

The alpha-2-adrenoreceptor antagonist yohimbine increases adrenergic activity and may provoke anxiety and panic symptoms in patients but no or only mild symptoms in healthy volunteers. Yohimbine infusions evoke intrusive symptoms, i.e. flashbacks together with significant increase of... 

Blockade of a2, Pi and p2-adrenoreceptors on LPS-stimulated alveolar macrophages reduces the release of interleukin (IL)-ip, IL-6 and cytokine-induced neutrophil chemoattractant-1. In this same condition, TNFa release is also strongly reduced by a2 and p2-adrenoreceptors antagonists. However, the blockade of a2-adrenoreceptors reached the most consistent suppression of the investigated cytokines (Flierl et al., 2007). 

The production of reactive oxygen species (ROS) is associated with cytotoxicity. In the CNS, microglia are an important source of these species. In neonatal hamster microglia stimulated with phorbol myristate acetate, a PKC activator, isoproterenol reduces the production of superoxide anion and this decrease was blocked by a P-adrenoreceptors antagonist (Colton and Chernyshev, 1996). 

Tomozawa et al. (Tomozawa et al., 1995) showed that isoproterenol induces IL-1 (3 mRNA in microglia, but not in astrocytes. This increase was inhibited by propranolol and by a cAMP-dependent protein kinase inhibitor. Similarly, NE, (31- and (32-adrcnorcccptors agonists produce an increase in IL-1 (3 mRNA, which is suppressed by (3i- and (32-adrenoreceptors antagonists (Tanaka et al., 2002). In line with those data, isoproterenol increases IL-la and IL-1 (3 mRNA in microglia (Hetier et al., 1991). On the other hand, these authors also showed that LPS-induced production of IL-1 P protein was inhibited by isoproterenol (Hetier et al., 1991). NE also decreases the production of IL-1(3 induced by LPS in miroglia (Dello Russo et al., 2004) (Madrigal et al., 2005). However, the reasons for these differences among the studies are still not clear. 

Tab. 4.17 Structural descriptors, physicochemical properties, and Caco-2 cell monolayer permeability coefficients of the P-adrenoreceptor antagonists (see Tab. 4.16). (Reprinted from Tab. 2 of ref. 54, with permission from the American Chemical Society)...

Prazosin (hydrochloride), 2-[4-(fur-2-oyl)piperazin-l-yl]-6,7-dimethoxy-4-quinazolinamine, a-adrenoreceptor antagonist antihypertensive [19216-56-9],... 

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