Brain receptor-targeting

A further brain receptor targeting vector is WAY 100635, which is directed toward 5-HTia receptor, one of the most thoroughly studied serotonergic receptors. The lead structure has been reduced as shown in Fig. 43.14 and derivatized with various chelators. 

Zhang, P., Johnson, P. S., Zollner, C., et al. (1999) Mutation of human mu opioid receptor extracellular disulfide cysteine residues alters hgand binding but does not prevent receptor targeting to the cell plasma membrane. Brain Res. Mol. Brain Res. 72, 195-204. 

GaiUard PJ, Brink A, de Boer AG. Diphtheria-toxin receptor-targeted brain drug delivery. Int Congress Series 2005 1277(ll) 185-98. 

The data presented above show clearly that GABA receptors of mammalian brain are targets for the toxic action of cyclodiene, yBHC and pyrethroids. Although, the binding and flux assays, used so sucessfully to study interactions of these insecticides with mammalian brain, have had limited success when applied to insect tissues, there is ample evidence to suggest that GABA receptors of insects are targets for AVM (7, 21) cyclodienes and pyrethroids (17, 22). 

Chronic antidepressant administration causes a chain of events, which begins with receptor targeting, intracellular second-messenger activation, gene expression, and the production of neurotrophic brain factors. These events modulate the neuroplasticity vital for the maintenance of normal mood and the resolution of the depressive mood. This chain of events corresponds chronologically to the resolution of depression, which usually takes at least 4 weeks. ... 

Harrison PJ (1999) Neurochemical alterations in schizophrenia affecting the putative receptor targets of atypical antipsychotics.Focus on dopamine (Di, D3, D4) and 5-HT2a receptors. Brain 122 593-624... 

Myr-TP-TF M5Tistic acid conjugated ceU-penetrating peptide with a transferring receptor targeted peptide Human murine neurons/ astroc tes 2 d siRNA 4 pmol/well Brain 71... 

BDNF (brain-derived neurotrophic factor) is a neuro-trophin, i.e. a target-derived growth factor, which is expressed in the brain predominantly in the hippocampus. It acts through its tyrosine kinase receptor, trkB,... 

The other important molecular target of ethanol is the N-methyl-D-apartate receptor (NMDA-R), which is acutely inhibited although the mechanism is not clear. It was speculated that at least in some brain region the coactivating glycine sites are involved and/or the coactivating polyamine sites. The receptors containing... 

Although MR also binds glucocorticoids, its main ligand in classical mineralocorticoid target tissues such as kidney and colon is aldosterone ( d 1.3 nM). This can be granted to the ability of 11 (3-hydioxysteroid dehydrogenase type II (11 (3-HSD II) to convert active cortisol into its inactive metabolite cortisone in these tissues. Since aldosterone is no substrate for this enzyme it can readily bind to MR, leading to exclusive occupation of the receptor by aldosterone. In contrast, no such mechanism exists in brain and presumably... 

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