0-Adrenoreceptor activity

Since TNFa and IL-6 are also important mediators in inflammatory responses, some work has also been done to investigate whether adrenoreceptors activation influences the production and release of these cytokines. TNFa, acting via two different receptors, p55 and p75, can present deleterious or protective effects in the CNS. There, it can be produced by microglia and astrocytes (Lucas et al., 2006). IL-6 has many functions in the CNS (see (Van Wagoner and Benveniste, 1999)). 

DeBock F, Kurz J, Azad SC, Parsons CG, Hapfelmeier G, et al. 2003. Alpha2-adrenoreceptor activation inhibits LTP and LTD in the basolateral amygdala Involvement of Gi/o-protein-mediated modulation of Ca2+-channels and inwardly rectifying K+-channels in LTD. Eur J Neurosci 17 1411-1424. 

Labetalol is a p-blocker with nonselective p- and selective Uj-adreno-receptor antagonist properties. With relatively high doses, labetalol elicits postural hypotension, an undesirable side-effect. Dilevalol is one of the four isomers (R, R) of labetalol that is almost devoid of a-adrenoreceptor activity. Hence, the reduction in peripheral vascular resistance observed for dilevalol occurs via its pj-agonist activity, which is not associated with postural hypotension. This renders dilevalol suitable for physically active hypertensive patients and those who complain of cold extremities (19). However, administration of dilevalol has been reported to be associated with a few reversible cases of hepatiris and jaundice (20). Hence, it is unlikely that this drug will become available as a new p-blocker. 

Activation of dopaminci (DA ) and dopamine2 (DA2) receptors reduces blood pressure. DA is not useful as an antihypertensive agent because of its alpha-adrenoreceptor activity. However, extensive studies in patients with hypertension have demonstrated that, after administration of alpha-adrenoreceptor-blocking agents, arterial pressure is decreased with maintenance or improvement of renal blood flow. 

Effect of N-Substltutlon on B-Adrenoreceptor Activity of Catecholamines. This subject has been carefully reviewed (e.g., 63). For this reason, it will not be reviewed in detail here. Generally, the influence of N-substitution on... 

Its presence in the absolute R stereochemistry at the benzylic position is essential for potent 6-adrenoreceptor activity. In all known instances, these are the levorotatory (-)-Isomers (22, 25, 30, 32, 63, 141). Generally, the S (+)-enantlo-mers have only weak 6-adrenerglc receptor activity. Interestingly, a-adrenerglc receptor agonist activity is described for R-isoproterenol whereas the S-isomer is an antagonist (51, 142, 143). 

Removal of the benzylic OH, i.e., to give a dopamine derivative markedly reduces 6-adrenerglc agonist activity (144, 145) to a level comparable to that of the less potent phenylethanolamlne enantiomer, an observation that has been rationalized at the receptor level (146). Replacement of the benzylic OH with a carbonyl group (123) results in a marked decrease in effectiveness in various tests for adrenoreceptor activity ( , 147). In the... 

Choi, Y. W. Rogers, J. A., The liposome as a model membrane in correlations of partitioning with a-adrenoreceptor against activities, Pharm. Res. 7, 508-512 (1990). 

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... 

The (R)-amino ketone is hydrogenated enantioselectively by a neutral complex [ (S)-(i )-BPPFOH RhCl]2 to give the (R,R)-isoproterenol analogue, a compound which has been shown to possess very potent /9-adrenoreceptor agonistic activity... 

---