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)

The effect of clonidine on a number of behavioural parameters believed to be expressed through central dopaminergic mechanisms has been studied in rodents. 1. Clonidine (0.06-2 mg/kg) potentiated the circling response to standard doses of both apomorphine (0.25 mg/kg) and amphetamine (3 mg/kg) in mice with unilateral destruction of nigro-neostriatal dopamine nerve terminals. Similarly, clonidine (0.06-2 mg/kg) enhanced the locomotor effect of apomorphine in reserpinised mice. 2. Clonidine (0.5 mg/kg) was without effect on the patterns of stereotypyd behaviours induced by the dopamine agonist apomorphine (0.1-5 mg/kg) in the rat. Unilateral intrastriatal injections of clonidine (5-100 microng) caused no discernable behavioural effects in rats. 3. Injection of apomorphine (10 microng) bilaterally into the region of the nucleus accumbens of the rat resulted in a hyperactive response, while bilateral injection of clonidine (50 microng) into this region caused marked sedation, thus mimicking the effects of these drugs on motor activity when administered systemically. Combinations of systemic or nucleus accumbens apomorphine and clonidine resulted in potentiated stereotype and prolonged hyperactivity responses. 4. Clonidine (0.5 mg/kg) potentiated the cataleptic effect of the dopamine antagonist haloperidol (0.1-2 mg/kg) in rats. Clonidine therefore potentiated those behavioural responses exhibiting a locomotor component (viz. circling and hyperactivity), but was without effect on stereotypy. The potentiation of catalepsy induced by clonidine may be explained in non-specific sedatory terms. It is apparent that clonidine acts through a secondary neurone system which modifies the effects of dopamine receptor stimulation, although the exact site of this interaction is not clear. The tentative conclusion might be that clonidine inhibits 5-HT neuronal activity, and the possible relationships between 5-HT and NA and dopamine are discussed.
 ...
PMID:The interaction of clonidine with dopamine-dependent behaviour in rodents. 55 29

Clonidine and methysergide constrict the rabbit auricular artery by activating smooth muscle alpha-adrenoceptors. Clonidine inhibits and methysergide enhances responses to stimulation of the sympathetic nerves. Both drugs sensitise the artery to a variety of vasoconstrictor stimuli, although not to potassium chloride. This weak generalised sensitisation may depend on clonidine and methysergide themselves being vasoconstrictor since sensitisation after clonidine did not occur when vasoconstriction was abolished with phentolamine. The marked potentiation of 5-HT and tryptamine observed during clonidine perfusion may reflect a property of the tryptamines since it was observed during perfusion with histamine but not when histamine vasoconstriction was abolished with mepyramine. Cyproheptadine and pizotifen neither constrict the artery nor sensitise it to vasoconstrictor agents. They inhibit responses to nerve stimulation, alpha-adrenoceptor agonists, potassium chloride and particularly histamine. Sensitisation of blood vessels reinforced by direct vasoconstriction may contribute to the mechanism of action of clonidine and methysergide in migraine. Conversely, alterations in vascular function may be less important to the antimigraine actions of either cyproheptadine or pizotifen.
 ...
PMID:Comparative effects of four migraine prophylactic drugs on an isolated extracranial artery. 126 90

Administration of various doses of clonidine increased plasma growth hormone levels. Pretreatment with the alpha 2 adrenergic antagonists, yohimbine and 1-(2-pyrimidyl)piperazine, completely blocked clonidine's effect on growth hormone levels. Pretreatment with the 5-hydroxytryptamine3 (5-HT3) receptor antagonist, MDL-72222, the 5-HT1A/5-HT2 antagonist, spiperone, and the mixed beta adrenergic/5-HT1B antagonists, l-propranolol and CGP361A, did not attenuate clonidine-induced increases in growth hormone levels. In contrast, pretreatment with the non-selective 5-HT1/2 antagonist, metergoline, and the 5-HT1C/5-HT2-selective antagonist, mesulergine, reduced clonidine-induced increases in growth hormone levels 81 to 87% without affecting clonidine-induced decreases in locomotor activity. Two other 5-HT1C/5-HT2 antagonists, ritanserin and mianserin, also attenuated (47%) clonidine-induced increases in growth hormone levels. Pretreatment with the noradrenergic neurotoxin, DSP4, did not block clonidine's effect on growth hormone levels. Clonidine administration decreased locomotor activity in both the Fawn-Hooded and the Wistar rat strains to the same extent. On the other hand, clonidine administration failed to increase growth hormone levels in the Fawn-Hooded rat strain. These findings suggest that clonidine stimulates growth hormone secretion by activation of alpha 2 adrenergic heteroreceptors present on 5-HT nerve terminals which, in turn, enhance 5-HT activity via stimulation of postsynaptic 5-HT1C receptors to promote growth hormone releasing factor. Furthermore, either 5-HT1C receptors or alpha 2 adrenergic heteroreceptors or both are functionally sub-sensitive in the Fawn-Hooded rat strain relative to the Wistar rat strain.
 ...
PMID:Functional subsensitivity of 5-hydroxytryptamine1C or alpha 2 adrenergic heteroreceptors mediating clonidine-induced growth hormone release in the Fawn-Hooded rat strain relative to the Wistar rat strain. 135 49

The effect of clonidine (0.1 mg/kg, i.p.), as a three-injection course, on behaviour in the forced swimming test was studied in rats injected intracerebroventricularly (i.c.v.) with 150 micrograms 5,7-dihydroxy-tryptamine (5,7-DHT) to destroy serotonin (5-HT) neurones or treated with 100 mg/kg (i.p.) (+/-)-sulpiride or 0.5 micrograms/0.5 microliter (-)-sulpiride in the nucleus accumbens. Clonidine significantly increased struggling and reduced floating and the effects were antagonized by both treatments with sulpiride but not by 5,7-DHT which markedly depleted 5-HT in brain. The results suggest that the mesolimbic dopaminergic system but not 5-HT neurones, plays a permissive role in the antidepressant-like effect of clonidine in the forced swimming test.
 ...
PMID:The role of serotonin and dopamine in brain in the antidepressant-like effect of clonidine in the forced swimming test. 152 50

Clonidine has been reported to be effective as an alpha 2-adrenoceptor agonist. Locomotor activity was measured by Automex after clonidine (100 micrograms/kg ip) administration. A significant reduction of locomotor activity was found during the 30th-45th-min period of experiment. 3-Methoxy-4-hydroxyphenylethyleneglycol (MHPG)-total was decreased significantly at 60 min after clonidine administration in rat cerebral cortex, hippocampus and hypothalamus. This might suggest that MHPG content at 60 min after clonidine administration can be used as functional index of the presynaptic alpha 2-adrenergic receptor. Desipramine (DMI) (20 mg/kg) was injected ip once daily for 14 d and experiments undertaken 60 min after the clonidine administration. Chronic DMI treatment had an effect on rat brain steady state levels of serotonin (5-HT) system. Chronic DMI administration was shown to attenuate the effect of clonidine that reduced MHPG levels on rat brain. The results suggest that the chronic DMI treatment may diminish the clonidine-induced reduction of MHPG via the subsensitivity of presynaptic alpha 2-adrenergic receptor.
 ...
PMID:[Effect of chronic desipramine treatment on rat brain adrenergic alpha 2-receptor]. 166 32

Changes in the function of presynaptic alpha 2-adrenoceptors in the brain were assessed by rating the hypoactivity (sedation) response of mice to clonidine (0.1 mg/kg). A single injection of 5,7-dihydroxytryptamine (5,7-DHT, 75 micrograms ICV) or administration of p-chlorophenylalanine (PCPA; 200 mg/kg) daily for 11-15 days produced 62-77% reductions in brain 5-HT concentrations and marked supersensitivity of 5-HT2 receptor function, as indicated by the enhancement of the head-twitch response to 5-methoxy-N,N-dimethyltryptamine (2 mg/kg). Clonidine-induced hypoactivity was moderately enhanced after 5,7-DHT lesioning, but not after repeated PCPA injection. In addition, 5,7-DHT lesioning prevented the adaptive attenuation of this alpha 2-adrenoceptor-mediated response produced by daily injection of desipramine (10 mg/kg) for 14 days, but had no effect on the reduction caused by five electroconvulsive shocks (ECS, 200 V, 2 s) spread over 10 days. In contrast, repeated PCPA treatment did not prevent the reduction of clonidine-induced hypoactivity produced by repeated desipramine or ECS administration. Together, these results indicate that 5-HT (or possibly a cotransmitter contained within 5-hydroxytryptamine neurones) influences presynaptic alpha 2-adrenoceptor function. Furthermore, an intact 5-HT neuronal input is a prerequisite for the attenuation of clonidine-induced hypoactivity by desipramine, but not ECS. The probable explanation for a contrasting requirement for a functional 5-HT input is that desipramine and ECS induce this common adaptive response by different pharmacological mechanisms.
 ...
PMID:An investigation of the role of 5-hydroxytryptamine in the attenuation of presynaptic alpha 2-adrenoceptor-mediated responses by antidepressant treatments. 216 Jun 63

Release of ATP can be evoked from noradrenergic nerve varicosities isolated from guinea pig ileal myenteric plexus by depolarization with K+ and veratridine and during exposure to acetylcholine or 5-HT. Clonidine, however, modulates the release of [3H]noradrenaline without affecting the release of ATP. ATP is also released from noradrenergic sympathetic nerves in the vas deferens, where it mediates the initial depolarization and contraction in the smooth muscle. Factors that apparently modulate the release of noradrenaline do not produce corresponding effects on ATP release. The above results are best explained by the hypothesis that ATP and noradrenaline are stored in separate populations of vesicles within sympathetic nerves and that these pools are subject to differential presynaptic modulation. Depolarization of rat brain synaptosomes releases adenosine by a process that is mediated, at least in part, by efflux on the nucleoside transporter. Drugs that block the nucleoside transport (such as dipyridamole) reduce evoked adenosine release and may thereby diminish, rather than augment, the actions of adenosine at its receptors. Release of adenosine does not appear to be uniformly distributed throughout the brain insofar as release varies from synaptosomes prepared from different regions. Although the distribution of several markers for possible adenosine pathways in the brain, including adenosine release, do not show any consistent correlations, the non-uniform distribution for these markers suggests that adenosine may have differential functions in various brain regions.
 ...
PMID:Neural release of ATP and adenosine. 229 28

Effects of apomorphine (APO) and clonidine (CLON) on the mesostriatal and mesolimbic serotonergic systems were examined in the present study. Both drugs selectively elevated serotonin (5-HT) concentrations in the dorsal raphe and the striatum without significantly altering 5-HT measures in the median raphe and the hippocampus. Apomorphine also increased tryptophan and 5-hydroxyindoleacetic acid (5-HIAA) levels in the dorsal raphe and 5-HIAA level in the striatum. Clonidine did not markedly alter tryptophan and 5-HIAA measures, while it decreased 5-HT turnover rate in both region, as indicated by the ratio of 5-HIAA/5-HT levels. Co-administration of APO and CLON, at doses of each drug exerted maximum effects on 5-HT alone, produced an additive effect on 5-HT in the dorsal raphe, while their effects on 5-HT and 5-HIAA in the striatum were counteracting each other. Effects of APO on 5-HT and 5-HIAA were attributed to the elevation of 5-HT precursor tryptophan, while effects of CLON on 5-HT and 5-HIAA were due to a decreased rate of 5-HT turnover. Therefore, the present results support the hypothesis that the additive effects of APO and CLON on dorsal raphe 5-HT are mediated through different receptors and neuropharmacological mechanisms.
 ...
PMID:Additive effects of apomorphine and clonidine on serotonin neurons in the dorsal raphe. 243 62

This experiment examined the necessity for intact noradrenergic and serotonergic function for the locomotor and nociceptive effects of clonidine in 10- and 100-day-old rats. Newborn rats were administered systemically 6-hydroxydopamine (100 micrograms/g; 12 and 24 hours after birth) to deplete norepinephrine (NE), and at 10 or 100 days they were injected with para-chlorophenylalanine (300 mg/kg PCPA; 5 and 24 hours before testing) to deplete serotonin (5-HT). They were then tested for the locomotor and analgesic effects of one of various clonidine doses (0, 10, 100 or 1000 micrograms/kg). Clonidine enhanced locomotion at 10 days. This effect was potentiated by NE depletion and reduced by 5-HT depletion. Clonidine reduced locomotion at 100 days, and again this was augmented by NE depletion but reduced by 5-HT depletion. NE depletion did not have an enduring effect on clonidine antinociception whereas 5-HT depletion reduced it at both ages. It is concluded that the locomotor effects of clonidine in both infant and adult rats, despite reversing with maturation, reflect its agonist action at postsynaptic alpha2 adrenoceptors. The results also add to the accumulating evidence for an early maturing and behaviorally relevant serotonergic system(s).
 ...
PMID:Noradrenergic and serotonergic mediation of the locomotor and antinociceptive effects of clonidine in infant and adult rats. 253 89

Intraperitoneal (i.p.) injection of the alpha 2-adrenoceptor agonist clonidine (1-3000 micrograms/kg) produced dose-dependent pupil dilatation in conscious C57/Bl/6 mice with an ED50 of 54 micrograms/kg (95% confidence limits 40-74 micrograms/kg). This response was rapid in onset and of approximately 30 min duration. The alpha 2-adrenoceptor antagonists idazoxan (1 or 3 mg/kg i.p.) and yohimbine (1 or 3 mg/kg i.p.) both produced dose-related miosis, but the alpha 1- and beta-adrenoceptor antagonists prazosin (1 or 3 mg/kg i.p.) and pindolol (1 or 3 mg/kg i.p.) were without effect. These doses of idazoxan and yohimbine potently reversed the mydriasis induced by clonidine (100 micrograms/kg i.p.), while prazosin and pindolol were again ineffective. Clonidine-induced mydriasis was also unaltered by the 5-HT antagonists, methysergide (2.5 mg/kg i.p.) and ketanserin (0.1 mg/kg i.p.) or 0.1 mg/kg i.p. of the dopamine antagonists, haloperidol, SCH 23390 and BRL 34778. A dose of 0.25 microgram clonidine, which was ineffective when administered i.p., produced marked mydriasis after intracerebroventricular (i.c.v.) injection. In addition, the mydriasis produced by i.p. injection of clonidine (100 micrograms/kg) was abolished by i.c.v. dosing of 2.5 micrograms idazoxan or yohimbine, but again not by prazosin or pindolol. Together, these data provide strong evidence to indicate that clonidine-induced mydriasis is exclusively mediated via central alpha 2-adrenoceptors and that this response provides a useful model for studying the function of these receptors.
 ...
PMID:Clonidine produces mydriasis in conscious mice by activating central alpha 2-adrenoceptors. 257 24


1 2 3 4 5 6 Next >>