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)

The antinociceptive effects of three predominantly serotonergic reuptake inhibitors, alaproclate, citalopram and clomipramine, were examined in mice using the hot-plate, formalin and substance P tests. The effects were compared with those of the noradrenergic reuptake inhibitor, desipramine. Different profiles in the three nociceptive tests were found for all four drugs, using doses of 10 and 40 mg/kg. The selective serotonergic reuptake inhibitor, alaproclate, seemed to have the least antinociceptive effects, and was the only drug that was ineffective in the hot-plate test. The other selective drug, citalopram, had a stronger effect than alaproclate in the substance P test, but in the formalin test, both drugs were approximately equally effective. Clomipramine differed from citalopram by being more effective in the formalin test. These findings thus indicate that selective inhibitors of the uptake of 5-HT have weaker antinociceptive effects than less selective drugs. Desipramine seemed to be no less effective than the serotonergic drugs and was the most potent drug in the hot-plate test.
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PMID:Antinociceptive effects of serotonergic reuptake inhibitors in mice. 248 59

Recent reports suggest that a cholecystokinin (CCK)-related dysfunction may be a target by which drugs can modulate anxiety and panic disorders. In the present study, effects of subchronic (14 days) treatment with the monoamine uptake inhibitors nortriptyline (30 mumol/kg per day), amitriptyline (29 mumol/kg per day), clomipramine (32 mumol/kg per day) and alaproclate (39 mumol/kg per day), as well as with the benzodiazepine clonazepam (0.25 mumol/kg per day), on rat brain levels of CCK- and substance P-like immunoreactivity, were compared. The drugs were administered by continuous s.c. infusion using implanted osmotic pumps. The plasma concentrations of the monoamine uptake inhibitors were similar after 1 and 2 weeks of treatment, indicating that steady-state plasma levels had been reached during the first week. Treatment with clomipramine or clonazepam increased the CCK-like immunoreactivity level in the ventral tegmental area (by 64.4 +/- 28.8% and 105.1 +/- 28.8%, respectively) and in the cingulate cortex (by 30.3 +/- 10.1% and 36.0 +/- 11.8%, respectively) (P < 0.05 or P < 0.01). Clomipramine also significantly increased the CCK-like immunoreactivity level in the periaqueductal grey by 85.1 +/- 29.7%. Neither nortriptyline nor amitriptyline or alaproclate produced any significant alterations in the CCK- or substance P-like immunoreactivity levels in the areas examined. The present results may suggest that an altered utilization of CCK in limbic circuits could be of importance for the well documented clinical effect of clomipramine and clonazepam in panic disorders.
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PMID:Clomipramine and clonazepam increase cholecystokinin levels in rat ventral tegmental area and limbic regions. 752 11

Substance P (SP) is possibly involved in the pathophysiology of depression and anxiety. We investigated interactions between antidepressants on SP-induced effects and their potential calcium-blocking activity in the isolated guinea pig ileum. All the antidepressants tested, except pargyline, moclobemide, mianserin, and reboxetine, were able to inhibit in a concentration-dependent manner the contraction induced by 100 nmol/L SP. Clomipramine, fluoxetine, maprotiline, and amitriptyline (all at 3 mumol/L) flattened the concentration-response curves to SP, resulting in a reduction of up to 59%, 63%, 32%, and 23%, respectively, of the maximum contractile effect. All the antidepressants tested (3 mumol/L), except pargyline, moclobemide, and mianserin, produced a rightward parallel shift of the concentration-response curve to CaCl2. The L-type selective calcium blocker nifedipine and the T-type selective mibefradil showed similar behaviour against both agonists used, SP and CaCl2. The relative order of potency was nifedipine (pA2, 7.6 +/- 0.1) > clomipramine (pA2, 7.0 +/- 0.1) > fluoxetine (pKB, 6.5 +/- 0.1) = mibefradil (pKB, 6.6 +/- 0.1) > amitriptyline (pKB, 6.3 +/- 0.1) = maprotiline (pKB, 6.2 +/- 0.1) > fluvoxamine (pKB, 5.9 +/- 0.1). The data reported in the present study suggest that the antidepressants tested did not behave as competitive antagonists versus NK1-receptor subtypes, but their inhibitory action seems to be related to their calcium-blocking properties.
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PMID:Older versus newer antidepressants: substance P or calcium antagonism? 1806 1