Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: DrugBank:APRD00174 (Clonidine)
 2,411 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Spinal cords were maintained in vitro and suction electrodes used to record activity in lumbar 4 or 5 ventral roots. Stimulation of the latero-ventral aspect of the thoracic cord elicited fast and slow responses on the same and on the opposite side of the cord. There were 5 distinct responses: ipsilaterally a short latency (d ISL), a polysynaptic and a slow response, and contralaterally a fast (d CON FAST) and a slow response. The largest amplitude component, d ISL, may arise from stimulation of propriospinal neurones; the other responses may arise from stimulation of descending pathways. The slow responses had half decay times of 13-15 s and required a high intensity stimulus to elicit a maximal response. All 5 responses were blocked by 6-cyano-7-nitroquinoxaline-2,3-dione suggesting that kainate/AMPA receptors were involved in their generation. In addition, NMDA receptors were involved in generation of the slow responses. Potentiation of certain responses by the 5-HT2 antagonists, ketanserin, ritanserin and Lilly 53837, indicated that endogenous 5-HT was exerting a modulatory depression of these responses. In addition to eliciting the 5 responses, thoracic cord stimulation caused an inhibition of segmental reflexes evoked from the lumbar dorsal root. Exogenous 5-HT, 8-hydroxy-2-(di-n-propylamino) tetralin, 5-carboxamidotryptamine, dipropyl-5-carboxamido-tryptamine and methysergide depressed all or some of the descending responses. Blockade of adrenoceptors using yohimbine, idazoxan, prazosin or propranolol had no unequivocal effect suggesting that the release of endogenous catecholamines was minimal. Clonidine was a potent depressant of the slow responses.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:The pharmacology of descending responses evoked by thoracic stimulation in the neonatal rat spinal cord in vitro. 810 94

Past research has suggested that the paraventricular nucleus (PVN) of the hypothalamus is an important brain site mediating changes in feeding induced by drugs that modify 5-hydroxytryptamine (5-HT; serotonin) neurotransmission. To test this possibility, several experiments examined the impact of lesions of the PVN on both decreases and increases in feeding following treatment with 5-HT-acting drugs. Rats with free access to standard lab chow were given access also to a wet mash diet for 1 h each day. When intakes of this diet had stabilised, rats were divided into two groups: one group received bilateral radiofrequency lesions of the PVN, the other served as a sham-operated control group. The PVN-lesioned group consumed more lab chow and gained significantly more weight over a 10-week period than the control group. Clonidine stimulated feeding in the sham-operated group, but did not do so in the lesioned group. These findings confirmed that the PVN lesions disrupted the control of food intake, as well as body weight regulation. The indirect 5-HT agonists D-fenfluramine (0.63, 1.25 and 2.5 mg/kg) and fluoxetine (2.5, 5 and 10 mg/kg), and the 5-HT1 agonist 1-(m-trifluoromethylphenyl)piperazine (TFMPP, 0.63, 1.25 and 2.5 mg/kg) dose dependently reduced the intake of the wet mash diet in sham-operated animals. This action was not modified by the PVN lesions. The highest doses of D-fenfluramine and fluoxetine also suppressed intake of chow over the 23-h period subsequent to the wet mash presentations, but the magnitude of this effect was similar in sham-operated and PVN-lesioned animals.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Radiofrequency lesions of the PVN fail to modify the effects of serotonergic drugs on food intake. 811 76

The influence of some noradrenergic, 5-hydroxytryptaminergic and cholinergic agents on imipramine-induced seizures were investigated in mice. DL-threo-3,4-dihydroxyphenylserine (DOPS) and pargyline significantly potentiated imipramine-induced seizures. Phentolamine and prazosin significantly attenuated seizures elicited by imipramine and significantly attenuated the seizure-enhancing effect of DOPs. alpha-Methyl-p-tyrosine and reserpine significantly attenuated seizures induced by imipramine. Disulfiram significantly protected mice against imipramine-induced seizures. However, DOPS significantly potentiated seizures induced by imipramine in disulfiram-pretreated animals. Clonidine effectively protected mice against imipramine-induced seizures. Idazoxan, on the other hand, significantly potentiated seizures induced by imipramine and significantly antagonised the protective effect of clonidine against the seizures. 5-HTP, PCPA, cyproheptadine, mianserin, ketanserin and trazodone did not affect imipramine-induced seizures to any significant extent. Physostigmine antagonised seizures induced by imipramine while atropine significantly potentiated the seizures, and significantly attenuated the protective effect of physostigmine against the seizures. These data suggest that enhancement and attenuation of central noradrenergic and cholinergic neurotransmissions respectively, and not 5-HT mechanisms, may underlie imipramine-induced seizures in mice.
 ...
PMID:The involvement of noradrenaline, 5-hydroxytryptamine and acetylcholine in imipramine-induced seizures in mice. 822 1

The action of clonidine and xylazine to suppress constrictor responses to norepinephrine (NE) and phenylephrine was analysed in isolated, perfused dog and monkey lingual arteries. In both kinds of arteries, alpha 1-adrenoceptor agonists, NE and phenylephrine induced strong vasoconstrictor responses, whereas alpha 2-adrenoceptor agonists, clonidine and xylazine, produced only a slight but long-lasting increase in perfusion pressure. Pretreatment with bolus injections of 300 micrograms clonidine or 1000 micrograms xylazine caused a significant inhibition of vasoconstrictor responses to NE and phenylephrine and shifted the dose-responses curves to the right. Clonidine induced a more potent inhibition than did xylazine. However, neither clonidine nor xylazine pretreatment inhibited 5-HT- and KCl-induced vasoconstriction. In preparations preconstricted with phenylephrine, clonidine and xylazine induced vasodilatation dose relatedly, but in preparations preconstricted with prostaglandin F2 alpha (PGF2 alpha), clonidine and xylazine never induced vasodilatation but only vasoconstriction. The vasoconstrictor effect of clonidine was readily blocked by bunazosin (an alpha 1-adrenoceptor antagonist), but was not affected by midaglizole (an alpha 2-antagonist). It was now demonstrated that alpha 2-agonists act as partial agonists on alpha 1-adrenoceptors when added alone but antagonized alpha 1 activation by alpha 1-agonists, suggesting that alpha 2-agonists have a high affinity for alpha 1-adrenoceptors in isolated lingual arteries.
 ...
PMID:Dominant antagonistic action of alpha 2-adrenoceptor agonists on alpha 1-agonist-induced vasoconstriction. 838 Jul 69

1. We set out to elucidate the pharmacological mechanisms by which alpha 2-adrenoceptor and 5-HT-receptor ligands affect the haemodynamic response to acute central hypovolaemia in conscious rabbits. 2. Acute central hypovolaemia was produced by inflating an inferior vena caval cuff so that cardiac output fell at a constant rate of approximately 8.5% of its baseline level per min. 3. Drugs were administered into the fourth cerebral ventricle in either 154 mM NaCl (saline) or 20% w/v 2-hydroxypropyl-beta-cyclodextrin (beta-CDX). After vehicle treatments, the haemodynamic response to acute central hypovolaemia had the usual two phases. During Phase I, systemic vascular conductance fell in proportion to cardiac output so that mean arterial pressure fell by only 8 mmHg. Phase II commenced when cardiac output had fallen to approximately 60% of its baseline level, when vascular conductance rose abruptly and arterial pressure fell to < or = 40 mmHg. The haemodynamic response was not dependent on the vehicle used (saline or beta-CDX). 4. Methysergide delayed the occurrence of Phase II in a dose-dependent manner, and prevented it at a dose of 30- 600 nmol (geometric mean = 186 nmol). The effects and potency of methysergide were not dependent on the vehicle used, indicating that beta-CDX can be used as a vehicle for fourth ventricular administration of lipophilic drugs to conscious rabbits. Clonidine (10 nmol) reversed the effects of a critical dose of methysergide. 5. Phase II was also prevented by 8-hydroxy-2-(di-n-propylamino)tetralin (5-HT1A-selective agonist, geometric mean critical dose (range) = 13.1 (10-30) nmol), sumatriptan (5-HT1D-selective agonist, 72.1 (10-300) nmol), mesulergine (5-HT2/1C-selective antagonist, 173 (30-1000) nmol), idazoxan (alpha 2-adrenoceptor-selective antagonist, 548 (100-3000) nmol), and mianserin (5-HT2/1C-selective antagonist, 548 (100-3000) nmol). It was not affected by MDL 72222 (5-HT3-selective antagonist, 300 nmol) or ketanserin (5-HT2/1C-selective antagonist, 3000 nmol). 6. To characterize the nature of alpha 2-adrenoceptors in rabbit brainstem, we examined the binding of [3H]-rauwolscine to membrane homogenates of whole brainstem. [3H]-rauwolscine bound to a population of sites with the characteristics of alpha 2A-adrenoceptors. 7. From these results we suggest that activation of 5-HT1A receptors in the brainstem can prevent Phase II of the response to acute central hypovolaemia in conscious rabbits. Our results do not support the notion of an endogenous 5-hydroxytryptaminergic mechanism mediating Phase II. The mechanism by which the alpha 2-adrenoceptor antagonists yohimbine and idazoxan prevent Phase II remains to be elucidated. However, their potency relative to other 5-HT-receptor ligands indicates that an agonist action at 5-HT1A-receptors is more likely than an antagonist action at alpha 2-adrenoceptors.
 ...
PMID:Effects of 5-HT-receptor and alpha 2-adrenoceptor ligands on the haemodynamic response to acute central hypovolaemia in conscious rabbits. 838

The binding of a highly specific ligand for serotonin (5-HT) uptake sites, [3H]paroxetine, was studied in brain regions of normotensive Wistar-Kyoto rats (WKY) and spontaneous hypertensive rats (SHR). [3H]Paroxetine bound to a single, high affinity binding site in the brain. In midbrain, the density (Bmax values) of [3H]paroxetine binding were significantly reduced (27.16%) in SHR as compared to WKY. The affinity (Kd values) were found to be similar in SHR and WKY. The Kd and Bmax values of [3H]paroxetine binding were found to be similar in spinal cord, pons and medulla and cerebral cortex of WKY and SHR. The effect of centrally acting hypotensive agents, clonidine and centhaquin, on [3H]paroxetine binding was also determined and compared with imipramine, a known 5-HT uptake inhibitor. Clonidine did not displace [3H]paroxetine binding at any concentration (10(-4) to 10(-7) M). On the other hand, centhaquin, which produces hypotension similar to clonidine, could displace [3H]paroxetine binding in a concentration dependent manner. In cerebral cortex and brainstem (midbrain, pons and medulla) membranes, the IC50 values of imipramine and centhaquin for [3H]paroxetine binding were found to be similar in WKY and SHR. The IC50 of centhaquin in displacing paroxetine from 5-HT uptake sites, was 10 times lower in the cerebral cortex and 4 times lower in the brainstem membranes when compared to imipramine. Clonidine had no effect on 5-HT uptake sites. The results indicate that (1) the density of 5-HT uptake sites is reduced in the midbrain of hypertensive rats, and (2) centhaquin, a centrally acting hypotensive agent, acts on 5-HT transporter sites.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Central serotonergic uptake mechanisms in hypertensive rats: effects of clonidine and centhaquin. 845 71

The forced swimming test (FST) is a behavioral test used to predict the efficacy of antidepressant (AD) treatments. In the present study, it was found that, when combined with clonidine, lithium or quinine, subactive doses of several types of ADs (tricyclics, 5-HT uptake inhibitors and atypical ADs) produced anti-immobility effects in mice. Clonidine (0.06 mg/kg) was found to potentiate the AD-like effects of all the drugs tested in the FST. More interesting is the additivity of gepirone with lithium (1 mEq/l), and ondansetron with quinine (0.5 mg/kg). The results of the present study are in favour of the potentiation of AD activity by clonidine via 5-HT2 receptors, lithium through 5-HT1A receptors, and quinine through 5-HT3 receptors. Further studies to examine in detail which of these three 5-HT receptors or their subtypes is the most important in the actions of individual ADs are warranted.
 ...
PMID:Differential effects of clonidine, lithium and quinine in the forced swimming test in mice for antidepressants: possible roles of serotoninergic systems. 888 83

Dorsal medullary brain slices containing primarily the nucleus tractus solitarius (NTS) were obtained from normal or 40- to 50-day streptozotocin-diabetic rats and employed for superfusion studies of evoked transmitter release. Electrically stimulated (25 mA, 2-ms pulses, 3 Hz, 1 min) release of [3H]norepinephrine ([3H]NE) or [3H]5-hydroxytryptamine ([3H]5-HT) from 400-microns NTS slices stimulated at 75 min (S1) and 130 min (S2) resulted in S2/S1 release ratios that were not different between normal controls or diabetic control groups. Perfusion of normal [3H]NE-loaded slices with 0.1 mumol/l clonidine reduced the S2/S1 ratio by 23% (p < 0.05) which was uniform in the caudal, subpostremal, and intermediate segment levels of the NTS. In diabetic NTS slices, the S2/S1 ratio was significantly less reduced by clonidine in both the subpostremal (-3%) and intermediate (-11%) slice regions. Blockade of alpha 2-adrenoceptors with yohimbine (0.1 mumol/l) enhanced (p < 0.05) [3H]NE release (S2/S1 ratios) in slices from both normal and diabetic rats. Perfusion of [3H]NE-loaded slices with 5 mU/ml insulin did not affect S2 release. Evoked S2/S1 release ratios from NTS slices loaded with [3H]5-HT did not differ between normal control and diabetic control groups. Clonidine (0.1 mumol/l) reduced S2-evoked release in both normal (-30%) and diabetic (-44%) slices, but the groups were not different from each other. Superfusion with 5 mU/ml insulin did not alter S2/S1 ratios in normal [3H]5-HT loaded slices, but did increase the diabetic NTS slice S2/S1 ratio to 1.40 +/- 0.06 (p < 0.01). In summary, it appears that alpha 2-adrenoceptor-mediated inhibition of [3H]NE release in the NTS was selectively attenuated in a regionally specific manner in diabetic animals. Release inhibition may be associated with receptor downregulation in NTS regions associated with cardiovascular reflex transmission. Insulin superfusion augmented [3H]5-HT release in the diabetic NTS slices, possibly through increased transmitter synthesis or improved synaptic release.
 ...
PMID:Effect of insulin and clonidine on the evoked release of norepinephrine and serotonin from the nucleus tractus solitarius of the diabetic rat. 896 94

The aim of the present study was the investigation of pretreatment effects with clonidine (0.06 mg/kg, intraperitoneal [i.p.]), lithium (1 mEq, i.p.) or quinine (0.5 mg/kg, i.p.) on the activities of various drugs acting on noradrenergic and/or serotonergic systems in the mouse tail suspension test. Drugs used in the present study included: the tricyclic antidepressants imipramine and dothiepin, the heterocyclic antidepressant trazodone, the 5-HT reuptake inhibitor (SSRI) fluoxetine, the atypical antidepressants mianserin and iprindole, the 5-HT1A receptor agonist ipsapirone, the 5-HT2A/2C receptor antagonist ritanserin, and the 5-HT3 receptor antagonist ondansetron. Clonidine, lithium and quinine differentially enhanced the effects of several psychotropic/drugs administered at sub-active doses. The activity of iprindole (32 mg/kg, i.p.) was not potentiated by pretreatment with clonidine, lithium or quinine. Our results suggest that lithium exerted additive effects via postsynaptic 5-HT1A receptor activation, quinine via potassium ion channel blockade of 5-HT3 receptors, while clonidine did so primarily via action at 5-HT2 receptors.
 ...
PMID:Effects of pretreatment with clonidine, lithium and quinine on the activities of antidepressant drugs in the mouse tail suspension test. 934 90

Antidepressants differ in their effectiveness for treating attention-deficit/hyperactivity disorder (ADHD) in adults and children. None are as effective as psychostimulants for treating the attentional and cognitive symptoms, but they can help reduce impulsive and hyperactive behavior. Tricyclic antidepressants have well-demonstrated efficacy in treating behavioral symptoms, but desipramine should be avoided, at least in youths and adolescents (and perhaps adults), because safer tricyclics are available. Bupropion was effective in its few controlled trials, but tics and (especially in youth) skin rash limit its value. Venlafaxine appears effective, but controlled studies are needed. Serotonin selective reuptake inhibitors have not been tested in controlled trials, but they cause inconsistent changes, often aggravate ADHD symptoms, and can cause frontal apathy and disinhibition. Clonidine has not been adequately examined but seems to have small or uncertain effects. Psychostimulants remain the treatment of choice because of their unique effect on attention. Multimodal treatments (medications plus psychosocial) might not be more effective than medications alone.
 ...
PMID:Antidepressants in the treatment of attention-deficit/hyperactivity disorder. 941 43


<< Previous 1 2 3 4 5 6 Next >>