UMLS:C0011570 - FACTA Search

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Query: UMLS:C0011570 (depression)
172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects on GH and PRL secretion of several pharmacological agents known to modify central neurotransmitter action were determined in unanesthetized male rats. Phenoxybenzamine, an alpha-adrenergic blocker (5 mg/kg iv), abolished episodic GH secretion and caused elevation of serum PRL levels. Propranolol, a beta-adrenergic blocker (5 mg/kg iv), had no effect on GH secretion and caused a small but significant depression in PRL levels. Parachlorophenylalanine methyl ester, an inhibitor of tryptophan hydroxylase (300-350 mg/kg ip), resulted in significant inhibition of GH pulsatile secretion and suppressed PRL levels. Methysergide hydrogen maleinate (25 mg/kg iv), a serotonin receptor antagonist, also inhibited GH secretion, but produced a transient stimulation in PRL levels. Atropine sulfate (2 mg/kg iv) caused significant suppression in GH secretion, but had no effect on PRL. Picrotoxin, a gamma-aminobutyric acid antagonist, in a subconvulsive dose of 1-3 mg/kg iv, also depressed GH episodic secretion but did not affect PRL levels. These results indicate that several neurotransmitters, i.e., norepinephrine, serotonin, acetylcholine, and gamma-aminobutyric acid, found in high concentration in the hypothalamus, influence GH and PRL secretion.
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PMID:Neuropharmacological regulation of episodic growth hormone and prolactin secretion in the rat. 3 92

Metehysergide in total doses of 100, 200 and 400 micrograms injected into the fourth cerebral ventricle of cats potentiated the reflex bradycardic responses which were evoked by i.v. pressor doses of norepinephrine. Methysergide (400 micrograms) injected i.v., or intracerebroventricularly in vagotomized cats did not affect the reflex bradycardia. These results suggest that the enhancement of reflex vagal activation is due to an action of methysergide in the central nervous system. Intracerebroventricular methysergide significantly reduced the resting arterial pressure and heart rate, while i.v. administration caused only significant bradycardia. Carotid occlusion responses were depressed following both i.v. and intracerebroventricular methysergide. The magnitude of reductions in arterial pressure and heart rate following the injection of methysergide into the fourth cerebral ventricle were the same in vagotomized cats and in intact vagus preparations. It is suggested that depression of cardiovascular function is due to a central action of methysergide and is mediated by reduction in sympathetic outflow.
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PMID:Enhancement of reflex vagal bradycardia following intracerebroventricular administration of methysergide in cats. 51 Apr 2

1 The interaction of effects between 5-hydroxytryptamine (5-HT) and adenosine diphosphate (ADP) on human or rabbit platelets was investigated in vitro. The initial platelet shape change and their aggregation were measured in stirred, citrated platelet-rich plasma (PRP) at 37 degrees C by recording the rate and extent of changes in light scattering and light transmission. 2 Both the velocity and extent of aggregation and the velocity and extent of the rapid morphological change caused by ADP were enhanced by simultaneous addition of 5-HT. Methysergide but not imipramine inhibited the 5-HT effects. 3 Platelets were made refractory to the aggregating and shape changing effect of either ADP or 5-HT by repeated aggregation with the particular agent; platelets made refractory to ADP retained their responsiveness to 5-HT and platelets made refractory to 5-HT responded to ADP. Platelets pre-incubated for 3-10 min with 5-HT without aggregation showed greatly reduced aggregation on subsequent addition of ADP. Methysergide inhibited all the effects of 5-HT whilst imipramine was inactive. 4 When the shape change or aggregation of platelets induced by ADP was submaximal, addition of 5-HT increased it further. Pre-incubation of PRP with 5-HT before the addition of ADP resulted in failure of the secondary induction of aggregation or shape change by 5-HT. The secondary induction by 5-HT also did not occur in the presence of methysergide; imipramine had no inhibitory effect. Similar secondary induction of aggregation was shown by adrenaline injected during aggregation by ADP; the adrenaline effect was removed by phentolamine but not by propranolol. 5 Our results show that the initial change in shape of platelets and their aggregation can be induced by ADP or 5-HT in specific manner. The interaction of the effect of these substances on platelets can result in either increase in platelet sensitivity or, under certain conditions, decrease in platelet responsiveness. The increase or depression of platelet reactivity appears to be a highly specific effect and is probably mediated at specific receptors involved with platelet activation.
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PMID:Shape change and aggregation of blood platelets: interaction between the effects of adenosine and diphosphate, 5-hydroxytryptamine and adrenaline. 125 69

Twelve ergolines (O-acylated lysergol and dihydrolysergol-I derivatives) were synthesized to study their antagonism of 5-HT responses in comparison with methylsergide and LY 53857 [6-methyl-1-(1-methylethyl)-8 beta-ergoline carboxylic acid 2-hydroxy-1-methylpropyl-ester hydrogen maleate] in cylindrical segments of the isolated rat tail artery. With regard to (9.10-didehydro-6-methyl-8 beta-ergoline)methyl R,S-2-methylbutyrate, the most potent new ergoline derivative, we examined the phenomenon of insurmountable antagonism to 5-HT by methylsergide. O-Acylated lysergol and dihydrolysergol-I derivatives competitively antagonized 5-HT-induced contractions with calculated pA2 values of 7.30 +/- 0.42 for the weakest and 8.42 +/- 0.35 for the most potent ergoline derivative in this series. N1-isopropyl substitution did not generally enhance 5-HT2 receptor affinities but lowered affinities for alpha 1 adrenoceptors in rat aorta. Methysergide and LY 53857 were insurmountable antagonists of 5-HT in rat tail artery. Preincubation with (9.10-didehydro-6-methyl-8 beta-ergoline)methyl R,S-2-methylbutyrate (1 mumol/l) partially prevented the depression of 5-HT-induced contractions caused by methysergide (1-10 nmol/l). Methysergide (100 nmol/l) abolished the protective effect of (9.10-didehydro-6-methyl-8 beta-ergoline)methyl R,S-2-methylbutyrate. (9.10-Didehydro-6-methyl-8 beta-ergoline)methyl R,S-2-methylbutyrate (1 mumol/l), concomitantly incubated with methysergide (30 nmol/l), partially restored the maximum response to 5-HT that had been depressed by methysergide (30 nmol/l). Partial restoration could not be mimicked by washout of methysergide.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:O-acylated lysergol and dihydrolysergol-I derivatives as competitive antagonists of 5-HT at 5-HT2 receptors of rat tail artery. Allosteric modulation instead of pseudoirreversible inhibition. 132 Feb 7

The 5-hydroxytryptamine (5-HT)3 receptor blocking properties of YM060, [(R)-5-[(1-methyl-3-indolyl)carbonyl]-4,5,6,7-tetrahydro-1H- benzimidazole hydrochloride], were examined by electrophysiological and radioligand binding studies. Results were compared with those for ondansetron, granisetron and the enantiomer (S-form) of YM060. 5-HT and 2-methyl-5-HT, a selective 5-HT3 receptor agonist, induced dose-dependent depolarizations of rabbit nodose ganglion with ED50 values of 24.0 (19.9-29.1) and 40.1 (30.9-52.1) nmol, respectively (geometric mean, 95% CL). YM060, ondansetron, granisetron and the S-form dose-dependently inhibited 5-HT-induced depolarizations with IC50 values of 3.85 (2.47-5.98), 1.55 (1.26-1.91), 1.45 (1.18-1.79) and 13.5 (11.2-16.2) nM, respectively. Methysergide, a 5-HT1-like and 5-HT2 receptor antagonist, at a concentration of 10(-5) M had no effect on responses to 5-HT. YM060 up to 10(-5) M produced no significant depression of depolarizing responses to 1,1-dimethyl-4-phenylpiperazinium iodide and gamma-aminobutyric acid. YM060, ondansetron, granisetron and the S-form displaced specific binding of [3H]GR65630 to N1E-115 neuroblastoma cell membranes with Ki values of 0.091 (0.086-0.097), 7.03 (5.96-8.01), 2.02 (1.74-2.30) and 10.3 (9.96-10.6) nM, respectively. These results show that YM060, compared with ondansetron and granisetron, has considerably higher affinity for 5-HT3 receptors in N1E-115 cells and slightly less potent 5-HT3 receptor antagonistic activity in rabbit nodose ganglion. Moreover, the isomeric activity ratio (R-form/S-form) was approximately 112 in N1E-115 cells and no greater than 4 in the ganglion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characterization of YM060, a potent and selective 5-hydroxytryptamine3 receptor antagonist, in rabbit nodose ganglion and N1E-115 neuroblastoma cells. 146 24

Intracellular recordings were made from motoneurons in transverse spinal cord slices from immature (12-20 day) rats and the effects of 5-HT on dorsal root evoked excitatory (EPSPs) and inhibitory (IPSPs) postsynaptic potentials were assessed. With or without causing a membrane polarization, 5-HT (1-300 microM) depressed synaptic responses; the IC50 was 6 microM. The inhibitory effect was potentiated by the uptake inhibitor fluoxetine. The 5-HT1A/1B agonists 5-CT and 8-OH-DPAT and the 5-HT1B/1C agonist TFMPP reduced the synaptic responses as well, with an IC50 of 0.26, 2.2 and 0.28 microM, respectively. The synaptic depressant effect was not antagonized by methysergide (0.1-1 microM), ketanserin (1-5 microM) and MDL 72222 (1-10 microM). Methysergide alone diminished the synaptic responses in some of the motoneurons. Spiperone (1-10 microM) partially and fully antagonized the depressant effect of 5-HT and 8-OH-DPAT, but was ineffective against 5-CT and TFMPP. The 5-HT-induced synaptic depression was not accompanied by a concomitant reduction of glutamate-induced depolarizations; the latter were enhanced after repeated exposure to 5-HT in some motoneurons. Finally, 5-HT reduced the afterhyperpolarization following a single spike or a train of spikes. The results indicate that 5-HT inhibits synaptic responses in motoneurons via presynaptic 5-HT1 receptors, the activation of which reduces the liberation of excitatory and inhibitory transmitters from respective nerve endings.
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PMID:Serotonin via presynaptic 5-HT1 receptors attenuates synaptic transmission to immature rat motoneurons in vitro. 168 86

The effects of serotonin (5-HT) or methysergide (a 5-HT antagonist), given intraperitoneally 30 min beforehand, on ethanol-induced mucosal injury and mucosal blood flow were studied in rats. 5-HT itself dose dependently decreased the gastric mucosal mucus content and induced gastric damage in conscious animals. It also worsened ethanol-induced lesion formation but not mucus depletion. Methysergide pretreatment only prevented the former action. In the ex vivo chamber preparation, 5-HT lowered the gastric mucosal blood flow and produced mucosal damage in unconscious animals. It also potentiated ethanol-induced gastric injury and 5-HT release. Methysergide significantly prevented lesion formation and 5-HT release in ethanol-treated rats. Ethanol decreased the gastric mucosal blood flow in the mucosa which had been preincubated with HCl. This depression of gastric mucosal blood flow was further reduced by 5-HT, but was reversed by methysergide. The lesion-potentiating or -protecting actions of 5-HT or methysergide, respectively, suggest that the amine is involved in gastric mucosal damage by ethanol in rats.
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PMID:The role of serotonin in ethanol-induced gastric glandular damage in rats. 234 Sep 64

Intracellular recordings were made from neurons of rabbit vesical pelvic (parasympathetic) ganglia (VPG). Application of 5-hydroxytryptamine (5-HT, 0.3-30 microM) produced an initial depression followed by a long-lasting facilitation of the fast excitatory postsynaptic potential (e.p.s.p.) evoked by stimulation of the pelvic preganglionic nerve. The facilitation of nicotinic transmission lasted for 30-120 min, even when 5-HT was removed from the superfusing solution. 5-HT (0.3-30 microM) did not change the depolarization induced by a direct application of acetylcholine (ACh) to the VPG neurons pretreated with 1 microM atropine. 5-HT also caused an initial depression followed by an increase in the quantal content of the fast e.p.s.p. It is, therefore, suggested that diphasic effect of 5-HT on the nicotinic transmission is due mainly to a modulation of the ACh-release from presynaptic nerve terminals. Methysergide (5 microM), mianserin (5-30 microM) and ICS 205-930 (100-300 nM) did not antagonize the presynaptic actions of 5-HT on the nicotinic transmission, suggesting that the presynaptic 5-HT receptor may belong to a class of 5-HT1 subtypes. Spiperone (1 microM), a selective 5-HT1A antagonist, blocked the 5-HT-induced inhibition of the fast e.p.s.p. Under the effect of spiperone, the facilitation appeared soon after application of 5-HT. The facilitation of the fast e.p.s.p. may be mediated through a 5-HT1B or 5-HT1C subtype. Lowering temperature of the external solution eliminated the 5-HT-induced facilitation of the nicotinic transmission. Forskolin produced a presynaptic facilitation of the fast e.p.s.p., without producing an initial depression. 3-Isobutyl-1-methylxanthine (10 microM) potentiated the facilitatory action of 5-HT. Bath-application of dibutyryl cyclic adenosine monophosphate (cAMP) (1-6 mM) and 8-bromo-cyclic AMP (2-5 mM) mimicked the effect of 5-HT in producing the facilitation of the fast e.p.s.p.s. All data presented are consistent with the hypothesis that 5-HT, acting on presynaptic 5-HT1 receptors, causes a facilitation in the release of ACh from preganglionic nerve terminals possibly mediated through an activation of adenylate cyclase.
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PMID:5-Hydroxytryptamine produces presynaptic facilitation of cholinergic transmission in rabbit parasympathetic ganglia. 254 88

Previous work in this laboratory has suggested that antagonist action of 5-hydroxytryptamine2 (5-HT2) receptors and agonist action of 5-HT1 receptors results in antidepressant-like effects (increased reinforcement rate and decreased response rate) in rats performing under the differential-reinforcement-of-low-rate 72-sec schedule (DRL 72-s) of reinforcement. Serotonergic mediation of antidepressant drug effects on DRL 72-s behavior was assessed with a series of 5-HT agonists, and blockade of the effects of the antidepressant drugs clorgyline and fluoxetine (which presumably indirectly stimulate 5-HT1 receptors) was attempted in separate experiments with the 5-HT1 and 5-HT2 antagonist methysergide and the 5-HT neurotoxin 5,7-dihydroxytryptamine. Direct 5-HT1A agonists 8-hydroxy-2-(di-n-propylamino)tetralin and 5-methoxy-N,N-dimethyltryptamine and the 5-HT precursor 5-hydroxytryptophan all increased the reinforcement rate. The 5-HT1B and 5-HT1C agonists m-chlorophenylpiperazine and 1-(m-trifluoromethylphenyl)piperazine did not increase the reinforcement rate. The 5-HT2 agonist and 5-HT3 antagonist quipazine also did not increase the reinforcement rate. The monoamine oxidase inhibitor clorgyline and the 5-HT uptake inhibitor fluoxetine increased the reinforcement rate and decreased the response rate as seen with other antidepressant drugs on the DRL 72-s schedule. Methysergide antagonized the reinforcement rate increasing effects of both clorgyline and fluoxetine. Depletion of brain 5-HT with i.v.t. 5,7-dihydroxytryptamine blocked the antidepressant-like effects of clorgyline. These results suggest that central 5-HT1A receptors are involved in mediating the antidepressant-like effects of some drugs on DRL 72-s behavior. These results provide evidence that stimulation of 5-HT1A receptors and antagonism of 5-HT2 receptors lead to an antidepressant-like effect on the DRL 72-s schedule and implies that these two receptors may be important in mediating clinical drug effects in depression.
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PMID:Evidence for involvement of 5-hydroxytryptamine1 receptors in antidepressant-like drug effects on differential-reinforcement-of-low-rate 72-second behavior. 274 11

We investigated the mode of action of the potent antagonist ICI 170,809 in the 5-hydroxytryptamine (5-HT)2 receptor system of arterial smooth muscle. We used isolated preparations from rat tail artery and calf coronary artery with the endothelium rubbed off. In tail artery ICI 170,809 (0.3-30 nM) antagonized surmountably and nearly competitively the contractile effects of 5-HT (pKB = 10.0) and partially prevented the depression of 5-HT-induced contractions caused by methysergide. Increasing methysergide concentrations gradually prevented the protective effect of ICI 170,809. The combination of 30 nM ICI 170,809 with 300 nM of its demethylated analog ICI 169,369 (pKB = 8.8) caused surmountable blockade of the effects of 5-HT as expected from competition of the three drugs for the same receptor. In calf coronary artery ICI 170,809 (1-100 nM) reduced the maximum contractile response to 5-HT by 35% and caused competitive antagonism (pKB = 10.4) of the remaining 65% of the responses to 5-HT. ICI 169,369 (100 nM) completely prevented the depression of the maximum response to 5-HT caused by ICI 170,809. Methysergide (3 nM) depressed the maximum response to 5-HT by 65 and 30% in the absence and presence of ICI 170,809. The results are consistent with the existence of two interconvertible states R in equilibrium R' of the 5-HT2 receptor. The equilibrium of R in equilibrium R' is shifted toward R' by methysergide greater than ICI 170,809 much greater than ICI 169,369.
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PMID:Dimethylation of the activator ICI 169,369 results in a high-affinity partial deactivator, ICI 170,809, of the arterial 5-hydroxytryptamine2 receptor system. 276 Aug 51

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