Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Serotonin Agents”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed2002

Serotonin agents in the treatment of acquired brain injury.

BACKGROUND: The development of novel serotonin agents has led to an increased use of these medications throughout medical practice. An understanding of the basic pharmacological function of these agents is key to understanding their usefulness. Among persons with brain injury, serotonin agents have been used for the treatment of depression, panic disorder, obsessive-compulsive disorders, agitation, sleep disorders, and motor dysfunction. CONCLUSION: This article will review the mechanisms, efficacy, and side effects of serotonin agents with a focus on persons with brain injury.

Brain Injuries↗
PubMed2001

Treating premenstrual dysphoric disorder using serotonin agents.

Premenstrual syndrome (PMS) affects 20%-50% of all women. Premenstrual dysphoric disorder (PMDD), which can be conceptualized as a more severe variant of PMS, can affect 3%-9% of all women. Because a significant number of women suffer from premenstrual disorders and afflicted women may spend up to half the month suffering from symptoms, it is important to identify and provide effective treatment for such women. Historically, it has been difficult to distinguish premenstrual disorders from other depressive disorders, given the high comorbidity of the two disorders. Most studies attempt to remove this confounding factor by excluding women with concurrent depressive disorders. Despite the difficulties and limitations inherent in studying treatments for premenstrual disorders, most investigations support the use of serotonin agents in treating PMDD.

Female↗
PubMed1976

Modification of adrenal function by the anti-serotonin agent cyproheptadine.

The effect of the serotonin antagonist, cyproheptadine (Cypro), on metyrapone-induced stimulation of the pituitary-adrenal axis was evaluated in nine normal subjects. The subjects underwent standard oral metyrapone tests (750 mg every four h, for six doses) while taking no medications and while receiving oral Cypro (4 mg every six h). Cypro administration caused a significant reduction in: 1) baseline 17-hydroxycorticosteroid (17-OH) excretion (-31 +/- 7.2%), 2) the increase above baseline in 24 h 17-OH excretion on the day after metyrapone (-32 +/- 4.9%), 3) serum 11-deoxycortisol concentrations 8 h (-45 +/- 5.5%) and 24 h (-18 +/- 3.6%) after the first dose of metyrapone, and 4) plasma ACTH concentration 8 h (-32 +/- 8.2%) and 24 h (-22 +/- 8.0%) after the first dose of metyrapone. When compared with the control test, Cypro administration did not alter: 1) baseline 17-ketosteroid secretion, 2) the fall in serum cortisol concentration while taking metyrapone, 3) the serum free metyrapone concentration, 4) cortisol metabolism, 5) the adrenal response to ACTH, and 6) assay methods for measurement of serum and urinary corticosteroids. Our data suggest that Cypro can reduce pituitary-adrenal responsiveness by reducing plasma ACTH concentrations. If Cypro acts as a serotonin antagonist, our data lends support to the idea that serotoninergic mechanisms are important in the control of pituitary ACTH secretion in normal human subjects.

17-Hydroxycorticosteroids↗
PubMed1992

Structure-activity relationship studies of CNS agents. Part 4: 2-[3-(4-aryl-1-piperazinyl)propyl]-1,2,3,4-tetrahydro-beta-carbolin+ ++ -1-one derivatives as potential central anti-serotonin agents.

Seven derivatives of 1,2,3,4-tetrahydro-beta-carbolin-1-one have been prepared. Three of them showed significant central anti-serotonin activity, comparable with that of trazodone or etoperidone. Some structural features were found to be important for the central antiserotonin activity of the investigated class of compounds.

5-Hydroxytryptophan↗
PubMed1978

Effects of serotonin, of its biosynthetic precursors and of the anti-serotonin agent metergoline on the release of glucagon and insulin from rat pancreas.

We have evaluated the effect of serotonin (5-HT) and of its biosynthetic precursors 5-Hydroxytryptophan (5-HTP) and tryptophan (TRP) on the release of immunoreactive glucagon (IRG) and insulin (IRI) from isolated islets and pieces of pancrease of the rat. In isolated islets, 5-HT inhibited the IRI response to a high glucose concentration (3.0 mg/ml), without affecting the IRG response to either a low (0.5 mg/ml) or a high glucose concentration; TRP stimulated the IRG and IRI response to the low glucose concentration, while 5-HTP was ineffective. When pieces of pancreas were used, 5-HT and 5-HTP inhibited IRG response to both glucose concentrations, while IRI release was inhibited only by 5-HT. The anti-5-HT agent metergoline enhanced the release of IRG and IRI by pieces of pancreas at both glucose concentrations. The results indicate that exogenous and endogenous 5-HT inhibit basal as well as glucose-mediated IRG and IRI release; that isolated islets are less sensitive than pieces of pancreas to the inhibitory effect of 5-HT and that TRP acts as an amino acid and not as a precursor of 5-HT.

5-Hydroxytryptophan↗
PubMed1990

Serotonin agents in anxiety.

The side effects and unwanted or unnecessary ancillary pharmacological properties of benzodiazepine anxiolytic drugs resulted in a continuing search for new agents with improved profiles of activity. Buspirone was the first novel drug to emerge from this search in almost thirty years. Investigations into its mechanism of action revealed a key role for serotonin in the pharmacotherapy of anxiety. A variety of serotonergic agents are now in preclinical and clinical development as anxiolytics, including 5-HT1A partial agonists, 5-HT2 antagonists, and 5-HT3 antagonists. In addition to the new drugs which will be developed as a consequence of these investigations, their clinical efficacy will prompt the development of new animal models of psychopathology, leading us ever closer to a full understanding of the neurobiological substrates of anxiety. In addition, deployment of these new agents in the armamentaria of the clinician and the basic scientist will lead to new insights into the treatment of other disorders and the biochemical mechanisms by which the effects of these drugs are obtained.

Antidepressive Agents↗
PubMed1982

Non-steroidal anti-inflammatory drugs if combined with anti-histamine and anti-serotonin agents interfere with the bronchial and platelet effects of "platelet-activating factor" (PAF-acether).

The non-steroidal anti-inflammatory drugs (NSAID) indomethacin, aspirin and salicylic acid, as well as the anti-histamine, mepyramine, and the anti-serotonin, methysergide, fail to interfere with bronchoconstriction, thrombo-cytopenia and hypotension induced by platelet-activating factor (PAF-acether, 1-O-octadecyl-2-acetyl-sn-3-glycerylphosphorylcholine) in the guinea-pig. When one of the NSAID was given combined with mepyramine and with methysergide, bronchoconstriction was suppressed, but thrombocytopenia and hypotension persisted. Platelets prepared from blood collected from animals treated with the NSAID or with mepyramine and/or methysergide, aggregated to a similar extent to PAF-acether; however, the accompanying release of ATP was inhibited in those animals which had been treated with the drug combination effective in vivo against bronchoconstriction. In vitro application to platelets of the drugs effective in vivo and ex vivo was ineffective in blocking the platelet-release reaction. This suggests the existence of in vivo sites of action for the synergistic inhibitory activity of NSAID and anti-histamine/anti-serotonin drugs on bronchoconstriction and on platelet secretion. PAF-acether possible releases from the platelets a bronchoconstrictor component, distinguishable from thromboxane A2 and depleted by reserpine administration to the animals, which could account for the in vivo effects on the bronchopulmonary system.

Adenosine Triphosphate↗
PubMedDate not supplied

Acute ethanol intoxication during pregnancy: postnatal effects on the behavioral response to serotonin agents.

Pregnant wistar rats were treated on the eighth day of gestation (GD 8) with two IP injections, spaced by 4 h, of either ethanol (2.9 g/kg in 24% v/v saline solution, EG) or saline (SG). Other pregnant females did not received any type of IP injections (absolute control group, ACG). Offspring were tested at 45 or 90 days of age. At 45 days of age, EG showed an increased behavioral response (forepaw treading and hindlimb abduction) to the 5-HT1 agonist, 5-methoxy-N,N-dymethyltryptamine. In addition, an enhanced "wet-dog" shakes behavioral response to 5-HT2 agonist, 5-hydroxy-L-tryptophan, was also observed in EG as compared to ACG and SG. On the contrary, at 90 days, EG exhibited a diminished behavioral reactivity to 5-HT1 and 5-HT2 agonists as compared to SG. These results demonstrated that acute administration of ethanol on GD 8 induced long-lasting changes in the functioning of central serotonergic systems.

5-Hydroxytryptophan↗
PubMedDate not supplied

Effect of serotonin-acting agents on the serotonin content of immune cells. A peculiar observation.

The effect of the tryptophan hydroxylase inhibitor, PCPA methylester, the serotonin reuptake inhibitor fluoxetine and MAO-A inhibitor clorgyline on the serotonin content of rat immune cells was studied, using labelled antibodies and flow cytometry. Each molecule significantly increased in males the serotonin concentration of peritoneal lymphocytes and the monocyte-macrophage-granulocyte group (mo-gran), however the agents were ineffective towards mast cells. In females fluoxetine and clorgyline increased the serotonin concentration in peritoneal lymphocytes and mo-gran. Fluoxetine also increased the serotonin level in mast cells. Thymus was absolutely resistant to the drugs in both genders. The results call attention (1) to the reverse effect of serotonin-acting agents on immune cells, (2) to the influence of the milieu where the cell is located and (3) the effect of gender.

Animals↗
PubMed1980

Enhanced behavioural, electrocortical and hyperthermic effects of serotonin-like agents after impairment of serotonin transmission in fowl brain.

In adult fowls and in young chicks (Gallus domesticus) the effects were studied on body temperature, behaviour and electrocortical activity of 5-HT and other direct or indirect serotonin agonists given into the III cerebral ventricle in conditions of prolonged impairment of serotoninergic transmission. In chicks pretreated with 5,6-dihydroxytryptamine the subsequent intraventricular injection of 5-HT produced more intense and longer-lasting hyperthermic response and behavioural and electrocortical sleep. On the other hand fenfluramine given intraventricularly in fowls pretreated with 5,6-DHT did not produce significant body temperature and behavioural changes. After 14 and 21 day treatment with methysergide the subsequent administration of 5-HT, fenfluramine and quipazine produced in fowls an hyperthermic response and behavioural sleep more marked and longer-lasting than in control animals. The present experiments show that in conditions of chronic impairment of 5-HT function there is an enhanced behavioural and body temperature response to 5-HT and drugs acting by releasing endogenous 5-HT or 5-HT agonists.

5,6-Dihydroxytryptamine↗
PubMed1986

Sensitivity of a peptide-activated neuron in Aplysia to serotonin and cyclic AMP-relevant agents.

Serotonin depolarized Aplysia buccal motoneuron B16. The response could be obtained in high-magnesium/low-calcium medium, indicating a direct effect on B16 and supporting a putative monosynaptic input to B16 from the serotonergic metacerebral neurons. Similar depolarizing effects in high-magnesium/low-calcium medium were obtained in response to 8-bromo cyclic AMP, isobutylmethylxanthine, theophylline and forskolin. Tolbutamide, a putative inhibitor of cyclic AMP-dependent protein kinase, blocked or reversed responses of B16 to egg-laying hormone containing extracts and to serotonin. Serotonin and forskolin significantly increased the cyclic AMP content of buccal ganglia, whereas egg-laying hormone-containing extracts did not.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1994

Beyond the serotonin reuptake inhibitors: rationales for the development of new serotonergic agents.

Serotonin (5-HT) is a neurotransmitter involved in the regulation of mood, arousal, aggression, sleep, learning, nociceptions, nerve growth, and appetitive functions. Medications that act on 5-HT and its receptors have applications in the treatment of a variety of psychiatric disorders, among them depression, anxiety, psychoses, eating disorders, obsessive compulsive disorder, body dysmorphic disorder, posttraumatic stress disorder, and conditions associated with aggression. The clinical effects of these medications depend not only on their capacity to increase synaptic concentrations of 5-HT, but also on their effects on subtypes of 5-HT receptors and on other neurotransmitter systems. A new generation of drugs acting on specific 5-HT receptors has the advantage of a low frequency of adverse effects, applicability in mixed and complicated syndromes, and usefulness as probes of the psychobiology of mental disorders. An understanding of the specific actions of these medications on cellular communication and signaling makes it easier to predict their applications and disadvantages in specific clinical syndromes. The diverse applications of this new generation of drugs suggest a reconceptualization of the categorical approach to diagnosis and the addition of a more dimensional approach, at least to psychopharmacology.

Antidepressive Agents↗
PubMed2004

2-(2-(dimethylaminomethyl)phenoxy)-5-iodophenylamine: an improved serotonin transporter imaging agent.

Imaging serotonin transporters (SERT) is an emerging research tool potentially useful to cast light on the mechanisms of drug action as well as to monitor the treatment of depressed patients. We have prepared two new derivatives of 3, 2-(2-(dimethylaminomethyl)phenoxy)-5-iodophenylamine (4) and 2-(2-(dimethylaminomethyl)benzyl)-5-iodophenylamine (5) (K(i) for SERT = 0.37 and 48.6 nM, respectively). Both [(125)I]4 and [(125)I]5 displayed excellent brain uptakes in rats, and they showed a highest uptake in hypothalamus (between 60 and 240 min), a region populated with the highest density of SERT. The specific uptake of [(125)I]4 in the hypothalamus resulted in a target to nontarget ratio ([hypothalamus-cerebellum]/cerebellum) of 4.3 at 2 h. Autoradiography of rat brain sections (ex vivo at 2 h) of [(125)I]4 showed an excellent regional distribution pattern consistent with known SERT localization. These data suggest that [(123)I]4 may be useful for imaging SERT binding sites in the brain by single photon emission computed tomography (SPECT).

Aniline Compounds↗
PubMed1989

Design and synthesis of propranolol analogues as serotonergic agents.

Serotonin (5-HT) binds with nearly identical affinity at the various central 5-HT binding sites. Few agents bind with selectivity for 5-HT1A sites. The beta-adrenergic antagonist propranolol binds stereoselectively both at 5-HT1A and 5-HT1B sites (with a several-fold selectivity for the latter) and, whereas it is a 5-HT1A antagonist, it appears to be a 5-HT1B agonist. As such, it could serve as a lead compound for the development of new 5-HT1A and 5-HT1B agents. The purpose of the present study was to modify the structure of propranolol in such a manner so as to reduce its affinity for 5-HT1B and beta-adrenergic sites while, at the same time, retaining its affinity for 5-HT1A sites. Removal of the side-chain hydroxyl group of propranolol, and conversion of its secondary amine to a tertiary amine, reduced affinity for 5-HT1B and beta-adrenergic sites. In addition, shortening the side chain by one carbon atom resulted in compounds with affinity for hippocampal 5-HT1A sites comparable to that of racemic propranolol, but with a 30- to 500-fold lower affinity for 5-HT1B sites and a greater than 1000-fold lower affinity for beta-adrenergic sites. The results of these preliminary studies attest to the utility of this approach for the development of novel serotonergic agents.

Animals↗
PubMed1994

Serotonin, serotoninergic agents and their antagonists suppress humoral immune reaction in vitro.

Serotonin (5-HT), its derivative 5-methoxy-tryptamine (MeOT) and ergot-alkaloid dihydroergosine (DHESN) suppressed the immune reaction of mouse spleen cells against sheep erythrocytes in vitro (PFC assay). Ketanserin and propranolol, antagonists of 5-HT, also caused suppression. However, cells incubated with propranolol 20 min before 5-HT or MeOT produced as many plaques as the non-treated cells. Preincubation with ketanserin resulted in similar interference, but the reversal was not complete. It is concluded that serotonin and related agents probably affect several types of immunocompetent cells participating in successive stages of the PFC reaction. The antagonists probably interfered via 5-HT receptors, adrenergic receptors or both. Immunosuppression observed with serotoninergic agents and their antagonists draws attention to possible side effects of such drugs.

Animals↗
PubMed2002

Serotonin releasing agents. Neurochemical, therapeutic and adverse effects.

This review summarizes the neurochemical, therapeutic and adverse effects of serotonin (5-HT) releasing agents. The 5-HT releaser (plus minus)-fenfluramine is composed of two stereoisomers, (+)-fenfluramine and (minus sign)-fenfluramine, which are N-de-ethylated to yield the metabolites, (+)-norfenfluramine and (minus sign)-norfenfluramine. Fenfluramines and norfenfluramines are 5-HT transporter substrates and potent 5-HT releasers. Other 5-HT releasing agents include m-chlorophenylpiperazine (mCPP), a major metabolite of the antidepressant drug trazodone. Findings from in vitro and in vivo studies support the hypothesis that fenfluramines and mCPP release neuronal 5-HT via a non-exocytotic carrier-mediated exchange mechanism involving 5-HT transporters. (+)-Norfenfluramine is a potent 5-HT(2B) and 5-HT(2C) receptor agonist. The former activity may increase the risk of developing valvular heart disease (VHD), whereas the latter activity is implicated in the anorectic effect of systemic fenfluramine. Anorectic agents that increase the risk of developing primary pulmonary hypertension (PPH) share the common property of being 5-HT transporter substrates. However, these drugs vary considerably in their propensity to increase the risk of PPH. In this regard, neither trazodone nor mCPP is associated with PPH. Similarly, although some 5-HT substrates can deplete brain 5-HT (fenfluramine), others do not (mCPP). In addition to the established indication of obesity, 5-HT releasers may be helpful in treating psychiatric problems such as drug and alcohol dependence, depression and premenstrual syndrome. Viewed collectively, it seems possible to develop new medications that selectively release 5-HT without the adverse effects of PPH, VHD or neurotoxicity. Such agents may have utility in treating a variety of psychiatric disorders.

Animals↗