Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using an electromyographic technique, an ascending excitatory response was recorded "in vitro" in the presence of atropine in the cat small intestine up to 70 mm orally with respect to the site of repetitive transmural nerve stimulation. This non-cholinergic ascending excitatory response was characterized by an increase in the slow wave amplitude and spiking activity. This response was reversibly abolished by Tetrodotoxin (3,1 X 10(-6) M) but remained unchanged after exposure of the intestine to: Hexamethonium (4,9 X 10(-6) M) plus Tubocurarine (1,4 X 10(-5) M), Guanethidine (5 X 10(-7) to 5 X 10(-5) M), Domperidone (2,3 X 10(-7) to 2,3 X 10(-5) M), Naloxone (3 X 10(-7) to 3 X 10(-5) M), Methysergide (2,8 X 10(-7) to 2,8 X 10(-5) M), Metergoline (2,4 X 10(-5) M), Methiotepin (2,1 X 10(-5) M) and Mepyramine (2,3 X 10(-5) M). This response was unaffected by the substance P analogues, D-Pro2, D-Phe7, D-Trp9-Substance P (10(-5) M) or D-Pro2, D-Trp7-9-Substance P (10(-5) M) but was reversibly abolished after exposure of the intestine to substance P (10(-6) M). Moreover substance P still effectively abolished this response in the presence of any two of the above analogues. The results of the present study show that the non-cholinergic excitatory response elicited in the cat small intestine due to the activity of long ascending pathways probably involved substance P. The functional significance of this response is discussed.
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PMID:Non-cholinergic ascending excitatory response in the cat small intestine: possible involvement of substance P. 246 25

Antidepressant drugs represent the principal form of treatment for major depressive disorder. While there are a plethora of medications available for this task, current drugs have many shortcomings. In the face of these deficiencies there is an ongoing search for new agents. The search has been guided, in part, by drug design based on existing agents and their putative mechanism of action. This has been less than fruitful in addressing inadequacies of existing medications as it has not produced compounds which are novel in terms of pharmacological mechanisms. Recent insights from molecular biological approaches hold promise for the discovery of novel compounds, in particular the so-called neurogenesis hypothesis suggests novel therapeutic approaches. Although significantly modified over the years, the monoamine hypothesis of depression and antidepressant drug action still remains an important driving force behind the development of new compounds. Several recently marketed agents and some in early-phase development tend to conform to these existing mechanistic hypotheses. Clearly the place of these agents in the treatment of depression is dependent on issues such as short- and long-term safety and efficacy. Duloxetine has been developed as a dual monoamine re-uptake inhibitor. Agomelatine is a compound with major effects on the circadian system as well as effects on subtypes of the serotonin receptor system. While the mechanism of action of this compound is not certain, recent evidence would suggest that the drug exerts its effects through antagonist actions at serotonin receptors. Compounds based on the hypothalamic pituitary adrenal axis, substance P antagonism and other neuropeptides have potential application for the treatment of depression but require further development before that potential is realized.
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PMID:Prospects for the treatment of depression. 1668 61