Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085631 (agitation)
 12,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Decreases in cerebrospinal fluid (CSF) calcium accompany mood elevation and motor activation in depressed patients undergoing treatment with ECT, lithium, and total sleep deprivation. Similarly, decreases in CSF calcium occur during acute psychotic agitation or mania. On the other hand, periodic recurrences of such agitated states are accompanied at their onset by transient increases in serum calcium and phosphorus. Several observations suggest that such serum ion shifts may trigger the more enduring and opposite shifts in CSF calcium and, in turn, the manic behavior. Progressive restriction of dietary calcium was earlier reported to mitigate and finally abolish both rhythmic rises in serum calcium and periodic agitated episodes in one psychotic patient. Lithium, which decreases the efficiency of alimentary calcium absorption, may function similarly. Conversely, a modest oral calcium lactate supplement (approximately one additional Recommended Daily Allowance of dietary calcium) seemed to slightly intensify agitation in six patients. Dihydrotachysterol (DHT), an analogue of vitamin D, which more exactly mimics the increase in both serum calcium and phosphorus, appeared in at least one periodically psychotic patient to trigger and opposite shift in CSF calcium. Moreover, in eight patients, manic symptomatology appeared de novo or grew significantly and substantially worse during 2 to 6 weeks of oral DHT administration. On the other hand, in 12 patients, subcutaneous injections of synthetic salmon calcitonin (SCT) decreased serum calcium and phosphorus, increased CSF calcium, and decreased agitation while augmenting depressive symptomatology. SCT also decreased quantified motor activity, frequency and severity of periodic agitated episodes, serum CPK and prolactin, and nocturnal sleep, while DHT or calcium lactate had opposite effects on the same parameters.
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PMID:Calcium: bivalent cation in the bivalent psychoses. 47 21

The pharmacokinetic and pharmacodynamic properties of raclopride, a new antipsychotic, were investigated in 16 healthy men. Single 4 mg doses were administered as intravenous infusion, oral solution and 2 extended release (ER) formulations. Total plasma clearance was about 100 ml/min (6.0 L/h), of which renal clearance accounted for 0.2 ml/min, indicating extensive metabolism. The volume of distribution was 1.5 L/kg; mean absolute bioavailability was 65 to 67% following the oral solution and the ER formulations. A transient increase in plasma prolactin levels followed both the intravenous infusion and the oral solution. The ER formulations resulted in a lower increase, which appeared later. However, the area under the prolactin level curve was similar after administration of all dosage forms. The frequency and severity of the most commonly reported side effects (tiredness and restlessness) were higher after the intravenous infusion than after the ER capsules. These findings indicate that such capsules may be advantageous for clinical antipsychotic treatment with raclopride.
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PMID:Pharmacokinetics of raclopride formulations. Influence of prolactin and tolerability in healthy male volunteers. 155 Dec 92

1. The pharmacokinetics and pharmacodynamics of prochlorperazine (PCZ) have been studied in healthy young males following single 12.5 mg i.v. and 50 mg oral doses, and during repeated doses (25 mg twice daily) for 14 days. 2. Oral bioavailability was low and an N-desmethyl metabolite was detected. Plasma clearance was high (0.98 1 kg-1 h) and the volume of distribution was large (12.9 1 kg-1) after i.v. dosing. 3. The terminal elimination half-life of PCZ was 9 +/- 1 h and 8 +/- 2 h after i.v. and single oral dosing, respectively. The urinary recoveries of drug and metabolite were low. 4. Accumulation of PCZ and its metabolite occurred following repeated dosing. The half-life at the end of 14 days therapy was 18 +/- 4 h. 5. Postural tachycardia, decreased salivary flow, impaired psychomotor function and a diminished level of arousal were observed after intravenous PCZ. Similar effects, but of lower magnitude were observed after single oral doses. During chronic dosing postural tachycardia and antihistaminic effects were observed, the latter not being observed after single doses. 6. After single intravenous dosing the maximal drug effects occurred 2-4 h after peak plasma drug concentrations for all measures except for plasma prolactin and self-scored restlessness 7. An antagonist action at dopamine (D2), muscarinic-cholinergic and alpha-adrenoceptors is postulated after single doses, with antihistaminic effects during chronic dosing, possibly indicating the presence of an active metabolite.
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PMID:Clinical pharmacology of prochlorperazine in healthy young males. 176 59

To examine further the serotoninergic system in obsessive-compulsive disorder (OCD), the plasma concentrations of cortisol and prolactin and the behavioral responses after oral administration of MK-212 (6-chloro-2-[1-piperazinyl]-pyrazine), a serotonin agonist, and placebo were studied in 17 patients with OCD and nine normal controls. The two groups did not differ significantly in basal plasma prolactin or cortisol levels. Nevertheless, both the prolactin and cortisol response to oral administration of MK-212 (20 mg) were significantly blunted in the patients with OCD compared with those of the normal controls. MK-212 did not affect the intensity of OCD symptoms. However, MK-212, as compared with placebo, produced slight but statistically significant increases in self-ratings of nausea, dizziness, anxiety, feeling strange, and mixed feelings of calmness and restlessness, as well as depression and feeling high. These behavioral ratings were not significantly different in patients and normal controls. These findings are consistent with previous reports of diminished serotoninergic responsivity in OCD and raise the possibility of subsensitivity of at least some serotonin receptors in this disorder.
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PMID:Prolactin and cortisol responses to MK-212, a serotonin agonist, in obsessive-compulsive disorder. 220 27

The serotonin agonist m-chlorophenylpiperazine (mCPP) was administered intravenously to 12 patients with Alzheimer's disease and ten age-matched controls. It produced distinct behavioral effects in both treatment groups; however, significantly greater responsivity to mCPP was found in patients with Alzheimer's disease than in controls in measures of psychomotor activation, restlessness, and perceptual abnormalities. Significant and similar increases in plasma prolactin and cortisol levels were found in both patients with Alzheimer's disease and controls following the administration of mCPP vs placebo. Furthermore, blood pressure and pulse changes following mCPP were not significantly different between the groups. Elderly controls, however, did show a significantly greater temperature response following mCPP than did patients with Alzheimer's disease. The overall cognitive effects of mCPP were minimal; however, mCPP produced significantly greater worsening in recent memory and knowledge memory in patients with Alzheimer's disease than in controls. These findings could not be explained by pharmacokinetic differences across populations, because plasma concentrations of mCPP were similar in patients with Alzheimer's disease and controls. The increased behavioral responsivity but unchanged neuroendocrine or other physiologic responsivity to mCPP may be related to damaged brain serotonin neurons or other neuronal systems that interact with serotonin neurons that have been found in postmortem and biopsy studies of patients with Alzheimer's disease.
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PMID:Hyperresponsivity to the serotonin agonist m-chlorophenylpiperazine in Alzheimer's disease. A controlled study. 273 Feb 78

Long days initiate the hyperphagia, fat deposition, and nocturnal restlessness, characteristic of the vernal migratory state in white-crowned sparrows. Ovariectomy, when performed in November, but not when performed in January, prevented induction by long days (20L:4D) of vernal fat deposition, whereas autumnal fat deposition was not affected. This is consistent with results obtained previously with males. Very high plasma levels of luteinizing hormone (LH) after photostimulation of ovariectomized females did not interfere with fat deposition. During fat deposition, levels of prolactin were not different from short-day levels and similar in ovariectomized and control females. However, ovariectomy performed in November suppressed the maximum levels of prolactin produced by long-day stimulation and inhibited or disturbed postnuptial molt. These effects were absent when ovariectomy was performed in January. Long-day-induced prolactin levels were higher when birds were photostimulated during a later phase of the annual cycle. It is suggested that castration does not interfere with long-day-induced vernal fat deposition via reduced secretion of prolactin in the absence of ovarian hormones or via supernormal secretion of LH, but that vernal fat deposition, prolactin secretion, and postnuptial molt require the presence of ovarian hormones prior to photostimulation. Autumnal migratory fat deposition, which is part of the cluster of events associated with photorefractoriness, has no requirement for gonadal hormones.
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PMID:Effects of ovariectomy on long-day-induced premigratory fat deposition, plasma levels of luteinizing hormone and prolactin, and molt in white-crowned sparrows, Zonotrichia leucophrys gambelii. 319 64

The thyrotropin-releasing hormone (TRH) test was studied in 32 patients with acute major depressive disorder, 16 patients with recurrent unipolar (n = 8) or bipolar (n = 8) affective disorder in remission, and 22 healthy control subjects. Twenty-six of the 32 acutely ill patients were also studied when in remission. Outcome in these patients was correlated to serum levels of triiodothyronine (T3), 3,3',5'triiodothyronine (reverse T3), thyroxine (T4), thyroid-stimulating hormone (TSH), prolactin (PRL), melatonin, dexamethasone suppression test (DST) results, and clinical symptoms assessed by the Comprehensive Psychopathological Rating Scale (CPRS). The TSH response to TRH (delta TSH) was decreased in the acutely ill patients, but no difference was found between patients in remission and controls. The delta TSH was correlated to TSH but not to T3 and T4 levels in both acutely ill and control subjects. In the acutely ill group, delta TSH did not distinguish between patients with normal and abnormal DST results. Thus, abnormalities in the hypothalamic-pituitary-thyroid (HPT) axis are not correlated to abnormalities in the hypothalamic-pituitary-adrenal (HPA) axis. Moreover, delta TSH did not differentiate between melancholic (DSM-III) and nonmelancholic patients or between patients with primary and secondary depression. No correlation was found between delta TSH and CPRS scores. Patients with observable agitation greater than 0.25 points (item range 0-3) had higher levels of delta TSH than patients with lower levels. No significant correlation was found between delta TSH and seven specific symptom clusters on the CPRS. However, there was a possible relation between low delta TSH and violent suicide attempts or suicide. PRL levels did not distinguish acutely ill patients from controls. Finally, there was no significant regression between delta TSH and melatonin levels. The decrease in delta TSH seen in the acutely ill patients was too small to be of diagnostic value as a laboratory measure differentiating acutely ill and healthy subjects. The mechanism underlying the HPT alterations in acute major depressive disorder may be a desensitization of the TRH receptor in the thyrotrophs secondary to an increased endogenous TRH stimulation.
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PMID:Effect of TRH on TSH and prolactin levels in affective disorders. 392 33

The purpose of the present study was to investigate the effect of bromocriptine in single doses of 20 and 30 mg on the unwanted effects most frequently caused by neuroleptics: elevated prolactin levels and extrapyramidal disturbances. 111 chronic schizophrenics were included in the investigations, 58 of them being treated with haloperidol and 53 with chlorpromazine. It was found that a single dose of 30 mg bromocriptine brought about a statistically significant decrease in the prolactin levels of patients treated with haloperidol but produced no more than a downward tendency in patients receiving chlorpromazine (the initial prolactin levels of both groups of patients were equal.) The effect of bromocriptine on EPS disturbances was more marked in the chlorpromazine group, but side effects such as nausea and agitation also occurred more frequently in this group. These results show that there is no correlation between the reduction in prolactin levels produced by bromocriptine and an improvement in unwanted EPS effects. This supports the hypothesis that the effect of neuroleptics on the prolactin secreting cells of the anterior pituitary and their effect on the EPS are mediated by different sets of receptors.
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PMID:[Effect of high single doses of bromocriptine in schizophrenic patients with elevated serum prolactin levels and extrapyramidal side effects associated with neuroleptic treatment (author's transl)]. 611 Oct 93

After having reviewed the properties of calcitonin (Ct), a hormone involved in calcium-phosphate metabolism and bone turnover, mention is made of the effects of Ct at the level of the CNS and its role as a neuromediator interfering with endorphins, prolactin, dopamine and the Ca concentration of the CSF. Overall's rating scale was used to evaluate the effects of synthetic salmon Ct in nine subjects with severe depression syndromes refractory to normal therapy. The study demonstrated statistically significant improvements of the major symptoms (behavioural excitation, depression, agitation, anxiety and affectivity). The favourable results justify broader and more detailed studies involving the relationship between Ct and psychopathology.
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PMID:A preliminary study on the use of calcitonin in clinical psychopathology. 614 Nov 15

A 10-day random double-blind study on the effect of bromocriptine versus placebo in severe alcohol-withdrawal symptoms was conducted in 60 alcoholics. The effect of bromocriptine--a dopamine agonist--was significantly better than placebo in ameliorating the following symptoms: anxiety, restlessness, depression, tremor, sweating and nausea as well as the total score of these symptoms. Also in the evaluation of specific symptoms according to a symptom check list of psychiatric, behavioural and social aspects, and in a global evaluation, bromocriptine was clearly superior to placebo. Serum prolactin studied on the first and tenth day of the survey showed a significant increase occurring in the placebo-treated patients. Side effects related to the use of bromocriptine were negligible. Our findings support recent experimental evidence that alcohol-withdrawal symptoms, at least in part, are related to a transient dopaminergic dysfunction in the brain.
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PMID:Bromocriptine in the treatment of the alcohol-withdrawal syndrome. 676 59


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