Pharmacological literature

Membrane-associated receptors are linked to transducing proteins (like G-proteins) in the inner portion of the membrane. G-protein coupled receptor (GPCR) families comprise a major class of the receptors that are pharmacologically relevant, such as muscarinic acetyl choline receptors, adrenoceptors, dopamine receptors, serotonine, opiate, peptide hormone, purinerg receptors, and also sensory chemoreceptors. A large variety of subtypes are described in the pharmacological literature. 

The stereo-chemistry of retinol is well known in the pharmacological literature. However, conversion of retinol into Rhodonine introduces a heavy atom at an asymmetrical location in the structure and the resulting molecules are distinctly non-planar. 

Some might object... even though caffeine is demonstrably inferior to amphetamines for pilots, everyone knows that amphetamines are "addictive" and hence unsuitable for such use. Such people will be well advised to consult the pharmacological literature on caffeine, which has been thoroughly documented as an addictive drug... 

Dixon (46) reviewed the pharmacological literature relative to sparteine prior to 1924. He observed that this alkaloid stimulates respiration by increasing its rate and amplitude but then depresses it. 

The astronomical cost of new drug discovery is fueled primarily by two factors (a) Combinatoric explosion in the number of possible derivatives of a lead, and (b) Cost of the screening process. A chemical can be screened by three methods in vivo, in vitro, and finally in silico. The potential therapeutic activity and toxicity of a chemical have usually been assessed in the pharmacological literature using a set of physicochemical properties and bioassay results. Table 1 gives a partial and ever expanding list of such properties. 

The antagonism of bactericidal sulfanilamides by p-aminobenzoic acid (PABA), a precursor of the vitamin folic acid, has been well documented in the pharmacological literature. More recently, it was shown that the phytotoxic activity of asulam, a herbicidal sulfanilamide derivative, also results from an inhibition of the biosynthesis of the vitamin folic acid. " In particular, asulam inhibits competitively the enzyme 7,8-dihydropteroate synthase, which catalyzes the conversion of 2-amino-4-hydroxy-6-hydroxy-methyl-7,8-dihydropteridine and PABA to dihydropteroic acid, leading to folate depletion. A consequence of the depletion of folic acid derivatives is the buildup of intermediates of the de novo synthesis of purine nucleo-tides. ° Such intermediates include 5 -phosphoribosyl glycineamide (GAR) or 5 -phosphoribosyl-5-amino-4-imidazole (AICAR). The accumulation of GAR and AICAR in asulam-treated pea seedlings has been reported. 

Based on one current classification system, fourteen serotonin receptor subtypes have been described for the peripheral and central actions of 5-HT. A brief summary is provided in Table 18.1 but the reader is referred to the appropriate pharmacological literature for details. Only the 5-HT3 receptor is a ligand-gated ion channel the remaining subfamilies are G-protein coupled receptors. It is also worth noting that the situation is more complicated based on the presence of additional receptors which... 

Amitriptyline is considered a classic TCA and was launched soon after imipramine in 1961. It is widely prescrihed and most commonly descrihed side effects in the pharmacological literature are apphcahle to most of the remaining TCAs. Amitriptyline overdose is considered to he particularly dangerous. Nortriptyline is the demethylated metabolite and also rndividtrally available (Kg. 18.18). 

In 1987, the United States Food and Dmg Administration (FDA) approved the use of fluoxetine for the treatment of depression and this derivative is now considered to be the prototype of a dmg class called selective serotonin reuptake inhibitors (SSRIs). As the name suggests, this term refers to the reuptake blockage of serotonin into the pre-synaptic membrane in order to indirectly increase neurotransmitter availability. A number of these derivatives showed beneficial effects for the treatment of a variety of additional conditions such as obsessive-compulsive disorders (OCD), bulimia nervosa, anxiety disorders, obesity, anorexia, post-traumatic stress disorders (PTSD) and others. SSRIs have become the first-line therapy for depression, which is based on improved side effect profiles when compared with TCA derivatives or MAOIs. A number of adverse effects are described in the pharmacological literature and include sexual dysfunction. 

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