Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A review of the clinical efficacy of four structurally distinct antidepressant drugs is presented. Their antidepressant activity can be rationalised within current pharmacological hypotheses of drug action, despite markedly different effects on "in vitro" testing. Fluoxetine, a specific serotonin re-uptake inhibitor, has proven safe, effective treatment for depressive illness and may have a role to play in the treatment of obsessive-compulsive disorder and panic attacks. While it has few of the anticholinergic side effects of the tricyclic antidepressants, nausea, tremor, headache, weight loss, nervousness and sweating are side effects most frequently reported. Minaprine, a compound with weak MAO inhibiting properties and effects on serotonergic receptors, has clinical efficacy in the treatment of depression based on several comparative studies. It is claimed that minaprine lacks anticholinergic and sedative properties. Moclobemide, a specific, reversible inhibitor of MAO-A, has been extensively evaluated in depressive illness. The major advantage of this agent over other irreversible, non-specific MAO inhibitors, is the significant attenuation of the so-called "cheese effect" with doses of tyramine likely to be encountered in foodstuffs. Rolipram, a phosphodiesterase inhibitor, represents a new approach to antidepressant treatment. Limited clinical data suggest that the drug may be an effective antidepressant with few side effects. The place of these agents in therapy is yet to be established.
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PMID:New pharmacological approaches to the management of depression: from theory to clinical practice. 158 Aug 88

An increase of cyclic adenosine and guanosine monophosphate (cAMP and cGMP) level can be achieved by inhibition of phosphodiesterases (PDEs), which are the enzymes responsible for the conversion of these second messengers into the corresponding 5-monophosphate inactive counterparts. The high heterogeneity in PDE families and in their tissue distribution, as well as their different functional role, make these enzymes very attractive targets for medicinal chemists. The PDE 4 family is particularly abundant in immunocompetent cells, where an increase of cAMP leads to the inhibition of the synthesis and release of pro-inflammatory mediators, cytokines and active oxygen species. Moreover PDE 4 inhibitors are able to reduce bronchial smooth muscle tone in vitro and show bronchodilatory effects in vivo. Thus, the current therapy for asthma, which is based on a combination of beta(2) agonists and corticosteroids, could be replaced by treatment with PDE 4 inhibitors. This review mainly covers PDE 4 inhibitors structurally related to xanthines and Nitraquazone, which appear to be very attractive models for the synthesis of novel PDE 4 inhibitors potentially useful for the treatment of asthma, chronic pulmonary obstructive disease and some autoimmune diseases. These compounds could be devoid of the central side-effects (nausea, vomiting, headache) of the archetypal Rolipram, which hampered its development as a drug. The review also highlights the novel structural classes of PDE 4 inhibitors recently reported in the literature.
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PMID:Phosphodiesterase 4 inhibitors, structurally unrelated to rolipram, as promising agents for the treatment of asthma and other pathologies. 1088 26