Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0040822 (tremor)
 18,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Following the IV administration of d-methamphetamine (MA), rats showed slow head shaking (SHS) and stereotyped gnawing (SG) behaviors in a dose-dependent manner. Methysergide, cyrpoheptadine, and p-chlorophenylalanine given intracerebroventricularly (ICV) or systemically significantly blocked SHS behavior induced by 10 mg/kg MA. Combined administration of L-5-hydroxytryptophan and peripheral decarboxylase inhibitor (Ro 4-4602) enhanced SHS behavior. Tyrosine hydroxylase inhibitor (H44/68) blocked SG behaviors, but dopamine-beta-hydroxylase inhibitors (FLA 63 and U-14, 624) and combined administration of L-3,4-dihydroxyphenylalanine and Ro-4-4602 enhanced it. These drugs did not affect SHS behavior. Phentolamine, phenoxybenzamine, clonidine, isoproterenol, and propranolol given ICV or systemically showed no effect on either SHS or SG behaviors. These results suggest that SHS behavior is produced by the activation of seronergic neurons in the central nervous system and are consistent with the view that SG behaviors are mediated through the release of dopamine. Some neuroleptics inhibited SHS as well as SG behaviors, but the older of inhibitory activity of neuroleptics onSHS behavior was quite different from their effects on SG behaviors induced by MA or apomorphine.
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PMID:The involvement of serotonergic neurons in the central nervous system as the possible mechanism for slow head-shaking behavior induced by methamphetamine in rats. 11 84

Previous studies have established that a complex behavioral syndrome--consisting of tremor, rigidity, hindlimb abduction. Straub tail, lateral head weaving and reciprocal forepaw treading--is a specific reflection of the activity of central serotonin receptors. This syndrome was utilized in the present study to test for supersensitivity in the central serotonergic system. Specific destruction of central serotonin nerve terminals by intraventricular injection of 5,7-dihydroxytryptamine (5,7-DHT, 50 mug) in adult male rats pretreated with a catecholamine uptake blocking agent resulted in marked supersensitivity to serotonin precursors and agonists. The greatest degree of supersensitivity was observed in response to L-5-hydroxytryptophan, for which the ED50 for elicitation of the syndrome was 20% of the value for control rats. A lesser degree of supersensitivity was seen in response to L-tryptophan (following monoamine oxidase inhibition) and the direct-acting serotonin agonist, 5-methoxy-N,N-dimethyltryptamine, for which the ED50 was approximately 50% of the control value in both cases. Supersensitivity begins to develop within 24 hours and is relatively complete by 96 hours after 5,7-DHT. A marked subsensitivity to the serotonin releasing agent, fenfluramine, was found in 5,7-DHT-treated rats. In contrast to the marked supersensitivity to serotonin precursors and agonists which occurs following 5,7-DHT, chronic administration of a serotonin synthesis inhibitor, p-chlorophenylalanine (400 mg/kg every 3 days for a total of 24 days), did not produce supersensitivity to L-5-hydroxytryptophan or 5-methoxy-N,N-dimethyltryptamine. Possible pre- and postsynaptic mechanisms for the development of supersensitivity are discussed.
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PMID:Behavioral evidence for supersensitivity following destruction of central serotonergic nerve terminals by 5,7-dihydroxytryptamine. 13 25

In the rat, d-amphetamine sulfate (15--80 mg/kg) causes numerous behavioral effects including simultaneous side-to-side head weaving or head tremor, forepaw padding and splayed hindlimbs. These signs are strikingly similar to a behavioral syndrome caused by intense serotonin (5-HT) receptor activation. Experiments were designed to determine whether some of the numerous effects of amphetamine on behavior can be ascribed to actions of the drug on 5-HT mechanisms. Catecholamine depletion with alpha-methyl-p-tyrosine did not prevent the amphetamine syndrome. However, 5-HT depletion with 5,7-dihydroxytryptamine or with p-chlorophenylalanine did prevent the syndrome. The degree of syndrome inhibition by p-chlorophenylalanine was correlated with the extent of 5-HT depletion. Normal responsiveness to amphetamine in p-chlorophenylalanine-treated rats was restored by 5-hydroxytryptophan, the precursor of 5-HT. Furthermore, methysergide, a 5-HT receptor blocker, prevented the amphetamine syndrome, whereas catecholamine blockers, phenoxybenzamine and pimozide, were ineffective. The results suggest that when amphetamine causes the signs of the syndrome it does so by activating 5-HT receptors in the brain, probably by displacement of endogenous 5-HT.
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PMID:Evidence that serotonin mediates some behavioral effects of amphetamine. 30 99

The serotonin precursor, 5-hydroxytryptophan (5-HTP), can induce a behavioral syndrome characterized by rigidity, splayed feet, tremor, head weaving, salivation and forepaw treading. This response to 5-HTP was markedly potentiated in adult rats treated intracisternally with 5,7-dihydroxytryptamine (5,7-DHT) during development. Prevention of the 5,7-DHT-induced reduction of brain norepinephrine with pargyline or desipramine did not diminish the potentiation of 5-HTP, suggesting that noradrenergic fibers are not contributing to the altered 5-HTP response. It was also found that treatments with 5,7-DHT potentiated the release of prolactin and the disruption of responding in a fixed-ratio operant task induced by 5-HTP. Other experiments indicated that 5,7-DHT treatments potentiated 5-HTP without affecting the action of L-dihydroxyphenylalanine. In addition, administration of the decarboxylase inhibitor, R0-4-4602, at a dose that inhibits enzyme activity in brain, blocked the 5-HTP-induced behavioral syndrome in 5,7-DHT-treated rats, indicating that 5-HTP must be converted to serotonin for 5-HTP to alter behavior. Thus, the present studies indicate that destruction of serotonergic fibers during development can produce permanent changes in central serotonergic mechanisms.
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PMID:Behavioral and prolactin responses to 5-hydroxytryptophan in rats treated during development with 5,7-dihydroxytryptamine. 30 87

Intracisternal injection of 5,7-dihydroxytryptamine (5,7-DHT) following treatment with desmethylimipramine induced development of behavioral supersensitivity to the intraperitoneally administered serotonin precursor 5-hydroxytryptophan (5-HTP) in the mouse. This behavioral syndrome, characterized by tremor and muscle twitches (myoclonus), showed a clear dose-response relationship with 5,7-DHT as well as with 5-HTP. Mice lesioned with a low dose of 5,7-DHT (20 micrograms) or a placebo were treated repeatedly with a protein synthesis inhibitor, sycloheximide (45 mg/kg, s.c., every 12 h for up to 10 days). This treatment resulted in a reversible decrease of cerebral protein synthesis varying between 70 and 20% with time between treatments. The myoclonic response to 5-HTP in animals pretreated with 5,7-DHT and by cycloheximide showed a decrease in intensity within 24 h when evaluated quantitatively by an electronic activity monitor, the results of which were confirmed by direct observation. Cycloheximide also exerted a similar, though smaller, effect following full development of sensitivity to 5-HTP over 10 days. These effects may de mediated by inhibition of rapidly turning over serotonin receptor proteins, although their interpretation is somewhat obscured by possible toxic effects of cycloheximide.
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PMID:Inhibition of 5,7-dihydroxytryptamine-induced supersensitivity to 5-hydroxytryptophan in mice by treatment with cycloheximide. 31 Mar 31

Phenoxybenzamine (5 mg/kg IP) and trazodone (5 mg/kg IP) reduced tremors produced in mice by administration of oxotremorine (10 mg/kg), harmaline (80 mg/kg), catechol (60 mg/kg), kepone (200 mg/kg) and clonidine (100 mg/kg). Azapetine (10 mg/kg IP) in combination with L-5-hydroxytryptophan (50 mg/kg IP) reduced the tremor induced by oxotremorine, catechol, kepone and clonidine. In mice with lower thoracic spinal cord transection, phenoxybenzamine and trazodone reduced catechol-induced tremor above and below the site of transection. These findings suggest that an alpha noradrenergic-serotonergic neuronal balance in the spinal cord may modulate tremors of different etiologies.
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PMID:Serotonin-norepinephrine interactions in the tremorolytic actions of phenoxybenzamine and trazodone. 31 3

In the last few years several open studies supported the hypothesis that L-5-HTP may be an effective antidepressant. Because of the lack of a controlled double-blind trial we started our own investigations to confirm this hypothesis in L-5-HTP. In 1972 we performed two open dose finding trials with L-5-HTP in combination with Benzerazide. These open studies were followed by a double-blind trial comparing L-5-HTP in combination with Benzerazide to Imipramine in 30 patients. Assessments were carried out on day 0, 5, 10, 15 and 20. For data collection we used the Hamilton Rating Scale for Depression, the AMP-system, a Global Rating Scale of Severity of Depression and a Brief Rating Scale for the Behaviour on the ward. In this article we report only a part of the results, mainly on the findings with the AMP-system and the Hamilton Rating Scale for Depression. During our double-blind trial we could not find any significant difference in efficacy of L-5-HTP and Imipramine. The same was found in an open trial. Furthermore the L-5-HTP results showed no difference compared with the results of an Imipramine treatment in 40 patients in earlier double-blind studies. L-5-HTP and Imipramine caused different patterns of side effects. L-5-HTP caused mainly gastrointestinal side effects and Imipramine caused mainly dryness of the mouth and tremor. The gastrointestinal side effects caused by L-5-HTP seemed to be dose dependent.
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PMID:The treatment of depression with L-5-hydroxytryptophan versus imipramine. Results of two open and one double-blind study. 33 2

Three major metabolites (M1, M2, M3) of nomifensine (8-amino-1,2,3,4-tetrahydro-2-methyl-4-phenyl-isoquinoline) are formed by hydroxylation and methoxylation of the phenyl ring. They were compared with nomifensine 1. in various psychopharmacological tests in vivo, carried out in mice after oral or i.p. treatment and 2. in neurochemical in vitro studies, measuring inhibition of noradrenaline (NA), dopamine (DA), and serotonin (5-HT) uptake in rat brain synaptosomes. M1 (4'-hydroxy-nomifensine) was the most active metabolite, while M2 and M3 had little or no effect in pharmacological tests. M1 reversed reserpine hypothermia in doses greater than 2.5 mg/kg, antagonized tetrabenazine catalepsy (ED50 68 mg/kg) and reversed oxotremorine hypothermia (ED50 33 mg/kg). In these tests nomifensine was also active, being about 3-10 times more potent than M1. In contrast to nomifensine M1 had also serotoninergic activity, potentiating both phenelzine-induced twitching (ED50 11 mg/kg) and the anticonvulsant effect of 5-hydroxytryptophan. Moreover, M1 prolonged the hexobarbital sleeping time in doses greater than 10 mg/kg, prevented nicotine-induced convulsions (ED50 58 mg/kg) and reduced the oxotremorine tremor (ED50 59 mg/kg). The LD50 of M1 was 1100 mg/kg orally. In vitro M1 was equipotent with nomifensine in inhibiting DA uptake (IC50 1.5 x 10(-7) M) and twice as active in inhibiting NA uptake (IC50 1.1 x 10(-8) M). In contrast to nomifensine M1 was also a potent inhibitor of 5-HT uptake (IC50 3.3 x 10(-7) M). M2 and M3 were less active than M1 in all experiments.
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PMID:Pharmacological and biochemical studies with three metabolites of nomifensine. 40 62

Pharmacological stimulation of central serotonin (5-HT) receptors causes a behavioral syndrome characterized by simultaneous side-to-side head weaving or head tremor, forepaw padding and splayed hindlimbs. This syndrome has been proposed and used as a model for 5-HT receptor activity. Questions have been raised about the possible involvement of catecholamines. This study was designed to differentiate behavioral signs contributed by 5-HT from those that might be due to catecholamines. Depletion of catecholamines by alpha-methyl-p-tyrosine, or depletion of 5-HT by either p-chlorophenylalanine or 5,7-dihydroxytryptamine, did not prevent the syndrome caused by 5-methoxy-N,N-dimethyltryptamine, a 5-HT receptor agonist. Pretreatment with methysergide, but not phenoxybenzamine or pimozide, prevented the syndrome caused by 5-methoxy-N,N-dimethyltryptamine. Conversely, 5-HT depletion prevented the syndrome caused by monoamine oxidase inhibitor and levodopa; behavioral response was restored in p-chlorophenylalanine-pretreated rats by 5-hydroxytryptophan. Methysergide prevented the syndrome caused by monoamine oxidase inhibitor and levodopa, but phenoxybenzamine or pimozide did not. Intraventricular 5-HT or dopamine also caused the behavioral syndrome after monoamine oxidase inhibition. p-Chlorophenylalanine pretreatment prevented the syndrome caused by dopamine, but did not prevent the syndrome caused by 5-HT. Our results suggest that systemic levodopa or intraventricular dopamine produces the behavioral signs through 5-HT mechanisms; endogenous catecholamine mechanisms are not involved directly in either the cause or expression of the behavioral syndrome.
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PMID:Specificity of a rat behavioral model for serotonin receptor activation. 68 17

A myoclonic syndrome consisting of tremor, myoclonus, and seizures was produced following the systemic administration of 5-hydroxytryptophan to adult rats previously given intracisternal injections of 5,7-dihydroxytryptamine and systemic desmethylimipramine, but not in their controls. This behavioral response was blocked by pretreatment with the putative serotonin receptor blocking agents methysergide, lysergic acid diethylamide, and bromolysergic and diethylamide, as well as centrally effective doses of the aromatic amino acid decarboxylase inhibitor Ro4-4602. Blockers of receptors of other neurotransmitters had little effect. This neurologic response in the adult rat may be relevant to some forms of clinical myoclonus and may be useful in testing potential agonists and antagonists of serotonin receptors in the mammalian central nervous system.
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PMID:Myoclonus after 5-hydroxytryptophan in rats with lesions of indoleamine neurons in the central nervous system. 108 96


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