Tissue-selective action

Fig. 3.2. Potential genomic and nongenomic activation routes thatmaybe induced by natural or synthetic ER ligands. The hypotheses that explain the tissue-selective action of SERMs include (a) selective activation of ER subtypes, (b) different changes in the 3D configuration of the ligand-ER complex, (c) recruitment of coactivator and corepressor proteins, and (d) activation of alternative response elements in certain inducible genes...

Evans GL, Turner NY (1995) Tissue selective actions of estrogens analogs. Bone 17(Suppl 4) 181S-190S... 

Somjen D, Waisman A, Kaye AM (1996) Tissue selective action of tamoxifen methiodide, raloxifene and tamoxifen on creatine kinase B activity in vitro and in vivo. J Steroid Biochem Mol Biol 59(5-6) 389-396... 

Mulac-Jericevic, B. and Conneely, O.M. (2004) Reproductive tissue selective actions of progesterone receptors. Reproduction, 128, 139-146. 

SELECTIVE ESTROGEN RECEPTOR MODULATORS AND ANTIESTROGENS SERMs TAMOXIFEN, RALOXIFENE, AND TOREMIFENE Selective ER modulators, or SERMs, exert tissue-selective actions. Their pharmacological goal is to produce beneficial estrogenic actions in certain tissues (e.g., bone, brain, and Uver) but antagonist activity in others... 

Clomiphene Clomiphene is used to induce ovulation in anovulatory women who wish to become pregnant. It is a nonsteroidal compound with tissue-selective actions. By selectively blocking estrogen receptors in the pituitary, clomiphene reduces negative feedback and increases FSH and LH output. The increase in gonadotropins stimulates ovulation. 

Molecnlar Mechanisms of SERM Action as a Means of Understanding their Tissue-Selective Activities... 

Barusiban is a long-acting, selective antagonist of OTR that is in development for preterm labour. It has a 300-fold higher affinity for the OTR than for the Vi AR and hence more selective action than atosiban on myometrial tissues. The duration of action may be longer then that of atosiban, providing the convenience... 

A relevant finding of this study was the selective action of raloxifene on leiomyoma tissue highlighted by a significant increase in the difference be-... 

When a 1/2 to 2% solution of cocaine is injected into a mixed nerve or into the subdural canal, the selective action is very marked, so that there is complete anesthesia, without motor impairment. If the contact is prolonged, by stopping the circulation, or if stronger solutions are employed, the motor fibers become paralyzed, so that the difference is merely quantitative. A similar difference in the susceptibility of motor and sensory structures exists also for the alcohol group, aconitine, phenol, hydrocyanic acid, and for pressure, and even for the centrally acting narcotics, ether, etc. It is therefore a characteristic of nervous tissue rather than of cocaine. It is now generally... 

In moving to other classes of JH analogs, major departures from the farnesane skeleton have been reported in the form of phenyl ethers (22, Z3,2 ), cyclohexenes such as juvabione (25), and small peptides (26) as an extreme case of completely selective action on one family of bugs. The latter compounds are most remarkable for the pronounced differential activity of their optical enantiomers, in which one antipode is several thousand times more active biologically than the other (2 7). In connection with the peptides, it should be noted that there is no formal proof that these compounds exert their action as true mimics of juvenile hormones at the target tissue level. One may well ask whether these peptides act directly on the corpora allata glands as allatotropins. 

Cox PJ, Phillips BJ, Thomas P. 1976. Studies on the selective action of cyclophosphamide (NSC-26271). Inactivation of the hydroxylated metabolite by tissue-soluble enzymes. Cancer Treat Rep 60 321-326. 

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