Intracellular receptors drug interactions

Intracellular Receptors These receptors are in the cytoplasm or nucleus. Drugs or endogenous ligand molecules have to pass through the cell membrane (a lipid bUayer) to interact with these receptors. The molecules must be hydrophobic or coupled to a hydrophobic carrier to cross the cell membrane. 

The main drug targets are enzymes, intracellular receptors, and extracellular (cell surface) receptors. Drugs are normally designed to interact with these entities either as agonists or antagonists to achieve control over the disease pathway. 

The important receptors are GPCRs, ion channels, tyrosine kinases, and intracellular receptors. Refer also to Appendix 3 for specific functions of the drugs in interacting with receptors. 

Each cell is surrounded by a plasma membrane that separates the cytoplasmic contents of the cell, or the intracellular fluid, from the fluid outside the cell, the extracellular fluid. An important homeostatic function of this plasma membrane is to serve as a permeability barrier that insulates or protects the cytoplasm from immediate changes in the surrounding environment. Furthermore, it allows the cell to maintain a cytoplasmic composition very different from that of the extracellular fluid the functions of neurons and muscle cells depend on this difference. The plasma membrane also contains many enzymes and other components such as antigens and receptors that allow cells to interact with other cells, neurotransmitters, blood-borne substances such as hormones, and various other chemical substances, such as drugs. 

There are a variety of structural classes of compounds that are active against each phosphodiesterase, and evidence suggests that selective inhibitors of PDEs can be identified. The structural diversity of PDE inhibitors provides a multitude of opportunities for development of compounds with drug-like properties. Furthermore, phosphodiesterase inhibition, which avoids direct interaction of a compound with a cell surface or nuclear receptor, may circumvent some of the target selectivity issues that can complicate receptor-based therapeutic approaches. As noted above, the specific subcellular distribution of phosphodiesterase enzymes is a key feature of their ability to modulate intracellular signaling pathways. This localization of the enzyme may minimize non-specific target... 

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