Targeting mechanisms

The possible mechanisms for insertion and removal of glutamate receptors at synapses have been reviewed recently (Petralia et al., 1999d). Receptors may be incorporated into 

Tanso R, Fonnum F (1989) Stimulation of peripheral cholinergic nerves by glutamate indicates a new peripheral glutamate receptor. Eur J Pharmacol 764 93-102. 

Akazawa C, Shigemoto R, Bessho Y, Nakanishi S, Mizuno N (1994) Differential expression of five A-methyl-D-aspartate receptor subunit mRNAs in the cerebellum of developing and adult rats. J Comp Neurol 347 150-160. 

Allan BB, Balch WE (1999) Protein sorting by directed maturation of Golgi compartments. Science 285 63-66. 

Allison DW, Gelfand VI, Spector I, Craig AM (1998) Role of actin in anchoring postsynaptic receptors in cultured hippocampal neurons differential attachment of NMDA versus AMPA receptors. J Neurosci 7S 2423-2436. 

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Side effects commonly arise from exaggerated effects at the primary target (mechanism-based toxicity), problems with dosing, prolonged use, or cytotoxicity (i.e.,... 

Drugs Targets Mechanisms Functional Side effects... 

Compound Microbiai target Ceii target Mechanism of action Refs. 

Target Mechanism Administration (Site of Action) Potential Functional Effect Example... 

We have shown that polymeric micelles constmcted of block copolymers of poly(ethylene oxide) (PEG) and poly(L-asparate) containing the anticancer dmg (adriamycin, ADR) selectively accumulate at solid tumor sites by a passive targeting mechanism. This is likely due to the hydrophilicity of the outer PEG chains and micellar size (<100 nm) that allow selective tissue interactions [17,18]. Polymeric micelle size ranges are tailored during polymer synthesis steps. Carefully selection of block polymer chemistry and block lengths can produce micelles that inhibit nonselective scavenging by the reticuloendothelial system (RES) and can be utilized as targetable dmg... 

Thermoresponsive polymeric micelles with PIPAAm block copolymers can be expected to combine passive spatial targeting specificity with a stimuli-responsive targeting mechanism. We have developed LCSTs of PIPAAm chains with preservation of the thermoresponsive properties such as a phase transition rate by copolymerization with hydrophobic or hydrophilic comonomers into PIPAAm main chains. Micellar outer shell chains with the LCSTs adjusted between body temperature and hyperthermic temperature can play a dual role in micelle stabilization at a body temperature due to their hydrophilicity and initiation of drug release by hyperthermia resulting from outer shell structural deformation. Simultaneously, micelle interactions with cells could be enhanced at heated sites due... 

The combinatorial effects of such chemical variability of chromatin, can be used as an informational tool or to directly modulate the physical and thermodynamic constraints of this nucleoprotein assembly. In the first instance a chemical signature can be used as a targeting mechanism to allow the recognition of regulatory regions by traw -acting factors or by ATP-dependent (i.e., SWI/SNF) or... 

Fig. 2. Dynamic steps in the drug development cycle. As explained in the text, multiple strategies can be used for initial drug target discovery, and at various steps in validating the drug target, mechanisms of action, or defining biomarkers of response, new drug targets can emerge.

Heilig M, Egli M Pharmacologic treatment of alcohol dependence Target symptoms and target mechanisms. Pharmacol Ther 2006 111 855. 

Emulate the evolutionary egregious targeting mechanisms of certain pathogens the so-called killers as healers model. 

Holzer, P. Capsaicin cellular targets, mechanisms of action, and selectivity for thin sensory neurons, Pharmacol. Rev. 1991, 43, 143-201. 

After synthesis, many proteins are directed to particular locations in the cell. One targeting mechanism involves a peptide signal sequence,... 

As in mitochondria (Fig. 18-4) an array of different transport proteins are required. They are distinctly different from the mitochondrial transport proteins and involve their own unique targeting mechanisms.251-2533... 

Table 8.1 Future Potential Target Mechanisms of Anti-HIV Therapy...

Cells must ensure that each newly synthesized protein is sorted to its correct location where it can carry out the appropriate function. This process is called protein targeting. In a eukaryotic cell, the protein may be destined to stay in the cytosol, for example an enzyme involved in glycolysis (see Topic J3). Alternatively it may need to be targeted to an organelle (such as a mitochondrion, lysosome, peroxisome, chloroplast or the nucleus) or be inserted into the plasma membrane or exported out of the cell. In bacteria such as E. coli, the protein may stay in the cytosol, be inserted into the plasma membrane or the outer membrane, be sent to the space between these two membranes (the periplasmic space) or be exported from the cell. In both prokaryotes and eukaryotes, if a protein is destined for the cytosol, it is made on free ribosomes in the cytosol and released directly into the cytosol. If it is destined for other final locations, specific protein-targeting mechanisms are involved. 

Inoguchi, T., and H. Nawata. 2005. NAD(P)H oxidase activation a potential target mechanism for diabetic vascular complications, progressive beta-cell dysfunction and metabolic syndrome. Curr. Drug Targets. 6 495-501. 

Fig. 12. Experimental setup for observation A. (a) - channel scheme p - internal proton beam, Target - target mechanism, Col - collimator, MS - magnetic shield (b) - magnet and detectors M - poles of spectrometer magnet, VC — vacuum chamber, DC - drift chambers, H - scintillation hodoscopes, S,SM - scintillation counters, C -gas Cherenkov counters, Absorber - cast-iron absorber, MC - monitor counters...

Therapeutic Target, Mechanism of Action, and Clinical Indication 131... 

Designing an appropriate preclinical development program requires a complete understanding of the therapeutic target, mechanism of action, clinical... 

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