Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Despite extensive study of the effects of various pharmacological agents on the thyrotropin (TSH) and prolactin (PRL) responses to TRH challenge, the effect of serotoninergic agents remains inconclusive. We studied the effect of the serotonin antagonists methysergide (non-selective 5-HT1/5-HT2 blocker with dopaminergic properties) and ritanserin (selective 5-HT2 blocker) on the TSH and PRL responses to TRH stimulation in two groups of medication-free female depressed patients in a double-blind, within-subject design. Methysergide was found to decrease significantly the PRL response to TRH, while ritanserin had no effect. Neither compound influenced the TSH response. Results suggest that 5-HT2 mechanisms do not mediate the PRL and TSH responses to TRH challenge in depression. The reduction in PRL observed after methysergide is probably due to either 5-HT1 or dopaminergic mechanisms.
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PMID:Effects of methysergide and ritanserin on the prolactin and thyrotropin responses to TRH in depressed patients. 761 98

1. The ability of 5-hydroxytryptophan, 5-HT2 receptor antagonists and typical and atypical neuroleptic agents to modify behavioural responding to aversive situations was investigated in the mouse light/dark test and rat social interaction. 2. The administration of 5-hydroxytryptophan inhibited rat social interaction and the exploratory behaviour of mice in the light/dark test. 3. The 5-HT2 receptor antagonists, ketanserin, ritanserin, MDL11939, methysergide and RP62203, the neuroleptic agents, spiperone, haloperidol and benperidol, and the atypical neuroleptic agent, clozapine, when administered alone failed to modify mouse or rat behaviour. In contrast, when administered alone, sulpiride in rats and mice and thioridazine in rats disinhibited behaviour. 4. Methysergide, RP62203, ketanserin, ritanserin and MDL11939 antagonized the inhibitory effects of 5-hydroxytryptophan or reversed the inhibitory effects to one of disinhibition. 5. Low doses of spiperone (but not haloperidol or benperidol) also antagonized the inhibitory effects of 5-hydroxytryptophan in the rat but not the mouse. Higher doses of the three neuroleptic agents caused locomotor depression in both rats and mice which obscured any specific changes in behavioural responding to the aversive situations. 6. The disinhibitory profile of sulpiride in both mice and rats and thioridazine in rats was evident during their interaction with 5-hydroxytryptophan. Thioridazine in the mouse and clozapine in rats and mice also reversed the inhibitory effects of 5-hydroxytryptophan to one of disinhibition. 7. In summary, we present evidence that the atypical neuroleptic agents, thioridazine and clozapine, with their known affinity for the 5-HT2 receptors, can mimic the actions of reference 5-HT2 receptor antagonists to antagonize the inhibitory effects of 5-hydroxytryptophan in rodent models of anxiety. The results are intepreted in terms of drug action on different 5-HT2 and other 5-HT receptor subtypes. In addition, thioridazine and sulpiride have disinhibitory effects in their own right which remain to be explained.
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PMID:Behavioural interactions between 5-hydroxytryptophan, neuroleptic agents and 5-HT receptor antagonists in modifying rodent responding to aversive situations. 868 Jul 34

The effects of 5-hydroxytryptamine (5-HT) on the responses of red nucleus (RN) neurones to glutamate (glu) and its agonists were studied using a microiontophoretic technique in anaesthetised rats. Extracellular unitary recordings of RN neuronal activity showed that 5-HT application induced a significant and reversible depression of glu-evoked excitations in 85% of the RN units tested. This effect was independent of the action of the amine on background firing, which appeared enhanced in the majority of cases but was either depressed or uninfluenced in other cases. Microiontophoretic 5-HT also depressed the excitatory responses evoked in RN neurones by electrical stimulation of sensorimotor cortex. Methysergide application, which prevented the enhancing effects of 5-HT on the background firing, was scarcely effective in antagonising the depression of glu responses. In contrast, the serotonergic effects on the glu responses were reduced by the iontophoretically applied antagonist of 5-HT1A receptors, NAN-190. Microiontophoretic 5-HT was also able to influence the neuronal responses evoked by glu agonists quisqualate (quis) and N-methyl-D-aspartate (NMDA), acting on non-NMDA and NMDA receptors respectively. In fact 5-HT depressed quis-evoked excitations and induced mixed effects on NMDA responses, which were reduced in 45%, enhanced in 34% and unmodified in 21% of the units tested. These results suggest that 5-HT is able to modulate the motor glutamatergic input to RN by acting mostly on non-NMDA receptors. The modulation of non-NMDA and NMDA receptors by 5-HT in the RN appears significant and its functional meaning is discussed.
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PMID:5-Hydroxytryptamine modifies neuronal responses to glutamate in the red nucleus of the rat. 954 78

Serotonin (5-HT) may be inhibitory to micturition at a spinal level. A potential mechanism of action for serotonergic inhibition of bladder function is a depression of the ascending limb of the supraspinal reflex mediating micturition. Ascending activity evoked by pelvic nerve stimulation was recorded in the thoracic spinal cord of anesthetized cats. For comparison, spinal reflex activity evoked by pelvic nerve stimulation was recorded on the pudendal nerve. The effects of intrathecal administration of serotonergic agents were examined to determine whether spinal and supraspinal responses to bladder afferent activation were modulated by 5-HT. Methysergide (60 nmol), a non-selective serotonergic antagonist, increased ascending activity by 61+/-7% and depressed spinal reflex activity by 38+/-6%. Zatosetron (10 nmol), a 5-HT3 antagonist had a similar effect on both activities (increased by 93+/-24% and decreased by 77+/-7%, respectively). The effect on ascending activity of blocking 5-HT3 receptors was also confirmed with ICS 205930 and MDL 72222. 2-Methyl-5-HT (800 nmol), a 5-HT3 agonist, depressed ascending activity to 46+/-9% of control, but enhanced spinal reflex activity by 73+/-92%. These results demonstrate that stimulation of 5-HT3 and methysergide-sensitive 5-HT receptors can inhibit ascending activity and facilitate spinal reflex activity elicited by activation of bladder afferents. It is suggested that descending serotonergic pathways may participate in the spinal coordination of urinary continence.
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PMID:Serotonergic modulation of spinal ascending activity and sacral reflex activity evoked by pelvic nerve stimulation in cats. 966 94

The involvement of serotoninergic mechanisms in the central respiratory depression produced by hypoxia was studied in the newborn rat brainstem-spinal cord preparation. The respiratory frequency measured by the C4 ventral root activity was recorded. 5-HT (30 microM) superfusion elicited a rapid increase in respiratory frequency, prevented by a treatment with methysergide (a 5-HT(1/2) receptor antagonist) (40 microM). To investigate the possible participation of 5-HT in hypoxic respiratory depression, this concentration of methysergide was added to the bathing medium during hypoxia. Methysergide did not modify the decrease in respiratory frequency produced by hypoxia. In order to ensure that other 5-HT subtype receptors were not involved in hypoxic respiratory depression, 5-HT was added to the bath during hypoxic-methysergide tests; no effect on respiratory frequency was observed. These results suggest that in the newborn rat brainstem-spinal cord preparation, serotoninergic mechanisms are not involved in the elaboration of the in vitro respiratory response to hypoxia.
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PMID:5-HT acting on 5-HT(1/2) receptors does not participate in the in vitro hypoxic respiratory depression. 1153 96

Migraine prophylaxis is a stepwise procedure with lifestyle advice followed by consideration of medications. Patients should be advised to try to maintain a regular lifestyle, with regular sleep, meals, exercise, and management of stress, perhaps through relaxation techniques or other ways that are sensible for them. If this regimen does not adequately control their migraines, preventatives are indicated. Patients can choose between evidence-based nutraceuticals such as riboflavin, feverfew, butterbur, or coenzyme Q10, or more traditional pharmacotherapeutics. Medicine choices are somewhat limited by what is available in each country, but from the full range, the medicines of first choice are beta-adrenoceptor blockers, flunarizine, topiramate, and valproic acid. Beta-adrenoceptor blockers are particularly useful in patients also suffering from hypertension or tachycardia. Following recent studies, topiramate has become a first choice for episodic as well as chronic migraine. It is the only prophylactic drug that may lead to weight loss, but it is sometimes associated with adverse cognitive effects. Valproic acid and flunarizine also have very good prophylactic properties. However, valproic acid is often associated with adverse effects, and flunarizine is unavailable in many countries, including the United States. If sequential monotherapies are ineffective, combinations of first-line drugs should be tried before advancing to drugs of second choice, which are associated with more adverse effects or have less well-established prophylactic properties. Amitriptyline should be used carefully because of its anticholinergic effects, although it is useful in comorbid tension-type headache, depression, and sleep disorders. Methysergide is very effective, but it has been supplanted or even made unavailable in many countries because of its well-described association with retroperitoneal fibrosis. Pizotifen has a slightly better safety profile but is unavailable in the United States. Aspirin is particularly useful in patients needing platelet inhibitors for other medical conditions, but the risk of gastrointestinal bleeding must be considered. The prophylactic properties of magnesium, riboflavin, and coenzyme Q10 are low at best, but their lack of severe adverse effects makes them good treatment options. Magnesium may be particularly useful during pregnancy. Lisinopril and candesartan were shown to be effective in single trials and are preferable in patients with hypertension. Acupuncture may be another alternative; although controlled trials have failed to differentiate its effect from placebo, it is at least innocuous. Botulinum toxin A is not effective in the prophylaxis of episodic migraine.
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PMID:Update on the prophylaxis of migraine. 1832 96


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