Receptors ion channels and

Tab. 8.1 Receptors, ion channels and enzymes which are drug targets and show species differences.

While those work well which have a certain combination of effects at various receptors, ion channels and transporters, others vdth a cleaner profile do not have the same therapeutic effect. 

C. F. Zorumsky, K. E. Isenberg (1991). Insights into the structure and function of GABA-benzodiazepine receptors ion channels and psychiatry. Am. J. Psychiatry 148 162. 

Post RM, Ketter TA, Pazzaglia PJ, et al. Receptor, ion channel, and neuropeptide targets for drug development implications from the anticonvulsant model. Am Coll Neuropsychopharmacol Abstr Panels Posters 1992 Dec 9. 

They found that a strain of mice that lacks the gene for NPY—NPY knockout mice—consume more ethanol than control mice and are less sensitive to ethanol s sedative effects. As would be expected if increased concentrations of NPY in the brain make mice more sensitive to ethanol, a strain of mice that overexpresses NPY drinks less alcohol than the controls even though their total consumption of food and liquid is normal. Work with other transgenic knockout mice support the central role in ethanol responses of signaling molecules that have long been believed to be involved (eg, GABA A, glutamate, dopamine, opioid, and serotonin receptors) and has helped build the case for newer candidates such as NPY and cannabinoid receptors, ion channels, and protein kinase C. 

Chronic exposure of animals or cultured cells to alcohol elicits a multitude of adaptive responses involving neurotransmitters and their receptors, ion channels, and enzymes that participate in signal transduction pathways. Up-... 

Ethanol Multiple effects on neurotransmitter receptors, ion channels, and signaling pathways Antidote in methanol and ethylene glycol poisoning Zero-order metabolism duration depends on dose Toxicity Acutely, CNS depression and respiratory failure chronically, damage to many systems, including liver, pancreas, GI tract, and central and peripheral nervous systems Interactions Induces CYP2E1 Increased conversion of acetaminophen to toxic metabolite... 

Once the extracellular first messenger from the transmitting neuron has handed over a message to an intracellular second messenger of the receiving neuron, the message then penetrates deep inside the recipient cell in a complex molecular cascade, which reaches enzymes, receptors, ion channels, and ultimately DNA, in order to transmit the information of how the neurotransmitter from the transmitting... 

Dupriez, V.J. et al. 2002. Aequorin-based functional assays for G protein-coupled receptors, ion channels, and tyrosine kinase receptors. Recept. Chann. 8, 319-330. 

Assay developments for important target classes such as protein kinases and phosphatases, proteases, nuclear receptors, G protein-coupled receptors, ion channels, and heat shock proteins... 

Figure 14,12 Phosphoinositide cascade. The cleavage of phosphatidyl inositol 4,5-bisphosphate (PIP ) into diacyiglycerol (DAG) and inositol 1,4,5-trisphosphate (IP5) results in the release of calcium ions (due to the opening of the IP3 receptor ion channels) and the activation of protein kinase C (due to the binding of protein kinase C to free DAG in the membrane). Calcium ions bind to protein kinase C and help facilitate its activation.

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