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)

Behavioral effects of setiptiline, a new tetracyclic compound (1,2,3,4-tetrahydro-2-methyl-9H-dibenzo [3,4:6,7] cyclohepta [1,2-C] pyridine maleate), were investigated to determine its pharmacological characteristics as an antidepressant in rats and mice, as compared with amitriptyline, a tricyclic antidepressant, and promethazine, a neuroleptic possessing an antihistaminic profile. Setiptiline exerted a weak stimulatory action on ambulation, spontaneous motor-activity, observed by the open field method in rats and potentiated the stimulatory effects of methamphetamine. Setiptiline also shortened the duration of immobility in rats forced to swim and inhibited catalepsy induced by haloperidol, yawning by physostigmine, body shaking as well as head twitch by 5-hydroxytryptophan in combination with Ro4-4602 and body shaking by morphine-withdrawal in rats. On the other hand, the drug did not exhibit an antagonistic effect on the hypothermia produced by reserpine in mice. From the results, it is suggested that setiptiline seems to have antidepressive activities that are pharmacologically dissimilar to those of tricyclic antidepressants.
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PMID:[Behavioral effects of a new antidepressant, setiptiline]. 204 13

The mechanisms by which imipramine and dihydroergosine stimulate the 5-HT syndrome in rats and inhibit the head-twitch response in rats and mice were studied. Imipramine- and dihydroergosine-induced stimulation of the 5-HT syndrome was inhibited stereoselectively by propranolol, a high affinity ligand for 5-HT1 receptor sites, but not by ritanserin, a specific 5-HT2 receptor antagonist. (-)-Propranolol potentiated the inhibitory effect of imipramine, but not of dihydroergosine on the head-twitch response, while ritanserin was without effect. Neither imipramine nor dihydroergosine were able to stimulate the 5-HT syndrome in the animals pretreated with p-chlorophenylalanine. As expected, 8-OH-DPAT, a selective 5-HT1A receptor agonist, stimulated, and 5-HT1B agonists CGS 12066B and 1-(trifluoromethylphenyl)piperazine (TFMPP) failed to stimulate the 5-HT syndrome induced in rats by pargyline and 5-HTP administration. A higher dose of ritanserin inhibited the syndrome. While 8-OH-DPAT alone produced all behavioral components of the 5-HT syndrome, dihydroergosine or imipramine alone even at very high doses never produced tremor or a more intensive forepaw padding as seen when these drugs were given in combination with pargyline and 5-HTP. A single administration of (-)-propranolol also inhibited the head-twitch response. This effect lasted in mice longer than after ritanserin administration. In in vitro experiments dihydroergosine expressed approximately twenty-fold higher affinity for 3H-ketanserin binding sites than imipramine. The results suggest that imipramine and dihydroergosine possess two components--one stimulating the 5-HT syndrome in rats by a presynaptic, presumably 5-HT1A-mediated mechanism, and the other inhibiting 5-HT2 binding sites.
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PMID:Do imipramine and dihydroergosine possess two components--one stimulating 5-HT1 and the other inhibiting 5-HT2 receptors? 211 65

Rats immobilized for 2 h daily for 7 days showed an increased behavioral response (forepaw treading and hind-limb abduction) to 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) 24 h after the last stress session. An injection of naloxone before each stress session fully antagonized the increased behavioral reactivity to 5-MeODMT. Treatment with morphine or beta-endorphin associated with each immobilization session for 3 days produced a response to 5-MeODMT higher than that of animals subjected to immobilization only. Chronic immobilization for 7 days did not affect the shaking behavior induced by 5-hydroxytryptophan (5-HTP) 24 h after the last restraint session. These findings suggest that chronic stress may induce a selective adaptive change of the 5-HT1 site and activate an opioid mechanism that is most likely to be involved in the development of this adaptive change.
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PMID:Opioid involvement in the adaptive change of 5-HT1 receptors induced by chronic restraint. 213 14

To study the involvement of serotonin (5-HT) receptor subtypes in behavioral supersensitivity following neonatal 5,7-dihydroxytryptamine (5,7-DHT) lesions, we measured acute behavioral responses to a single dose of selective 5-HT1A (8-OH-DPAT) or 5-HT2,1C (DOI) agonist compared to 5-hydroxytryptophan (5-HTP) in rats injected with 5,7-DHT intraperitoneally or intracisternally 14 weeks earlier. Only intraperitoneal 5,7-DHT injection resulted in brainstem 5-HT hyperinnervation, but cortical 5-HT depletions were also less. Effects of DOI, such as shaking behavior and forepaw myoclonus, were enhanced by 5,7-DHT lesions made intracisternally not intraperitoneally, whereas 8-OH-DPAT-evoked behaviors, such as forepaw myoclonus and head weaving, were enhanced more by the intraperitoneal route. The main consequence of intraperitoneal compared to intracisternal 5,7-DHT injection on supersensitivity to 5-HT agonists was increased presynaptic 5-HT1A responses and decreased 5-HT2,1C responses. In contrast, 5-HTP evoked more shaking behavior and less of the serotonin syndrome with the intraperitoneal compared to the intracisternal route of 5,7-DHT injection. Behavioral supersensitivity to 5-HTP, which was attributable to 5-HT1A, 5-HT2,1C, and possibly to other 5-HT receptors, was orders of magnitude greater than that elicited by direct receptor agonists and more clearly differentiated between rats with 5,7-DHT lesions and their controls, and between routes of 5,7-DHT injections, than responses to 5-HT agonists at the dose studied. 5,7-DHT induced dysregulation of 5-HT receptors, including both presynaptic and postsynaptic changes and altered interactions between receptor subtypes, better explains these data than postsynaptic changes alone.
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PMID:The functional significance of neonatal 5,7-dihydroxytryptamine lesions in the rat: response to selective 5-HT1A and 5-HT2,1C agonists. 214 15

The effects of serotonergic substances on the locomotor pattern and cutaneous reflexes were studied in 3 adult chronic spinal cats trained for 1-3 months to walk with their hindlimbs on a treadmill. The 5-hydroxytryptamine (5-HT) precursor, 5-hydroxytryptophan (5-HTP), and two 5-HT agonists, 5-methoxy-N,N-dimethyltryptamine and quipazine, were found to generally increase the step length and augment the amplitude of hindlimb extensors and flexors as well as axial muscles. Correspondingly, the excursion of the hip, the knee and the ankle joints was increased, mainly in the flexion direction. Cyproheptadine, a 5-HT antagonist, partially or completely antagonised these effects. The threshold current needed to elicit a flexion reflex by stimulating the dorsum of the paw through implanted wires, was lower after the injection of 5-HT agonists than in the immediately preceding control period. Fast paw shaking initiated by dipping the paw in water was unchanged after quipazine and was not abolished by cyproheptadine. In accordance with others, our results suggest that serotonergic drugs may increase the excitability of several types of spinal neurones, including motoneurones, and consequently influence the locomotor pattern as well as the reflex responsiveness. The changes observed with serotonergic agonists were different in many respects from those obtained with noradrenergic agonists and these differences are discussed. This may indicate specific roles for these classes of substances on locomotor function and reflex activity and also provide a basis for further clinical investigations.
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PMID:The effects of serotonergic drugs on the locomotor pattern and on cutaneous reflexes of the adult chronic spinal cat. 235 31

Rat pups were injected intracisternally (i.c.) or intraperitoneally (i.p.) with 5,7-dihydroxytryptamine (5,7-DHT) or saline and challenged 2 and 14 weeks later with the 5-HT precursor 5-hydroxytryptophan (5-HTP), which evokes behavioral supersensitivity in adult rats, 5,7-DHT induced transient postinjection convulsions in rats injected i.c. but not i.p. Rats with either type of 5,7-DHT lesions displayed supersensitive behavioral responses to 5-HTP. However, rats lesioned by i.p. injections exhibited significantly greater shaking behavior (+1445%) in response to 5-HTP than their i.c. counterparts, who instead showed more forepaw myoclonus (+250%) and head weaving (+270%), the core features of the 5-HT syndrome. Differences in 5-HT syndrome behaviors were already present 2 weeks after lesioning, whereas the difference in shaking behavior was not. After 14 weeks, 5-HT was selectively depleted (-43 to -92%) in hippocampus, spinal cord, and frontal cortex, and differences between i.c. and i.p. 5,7-DHT routes were insignificant except in frontal cortex. Brainstem 5-HT concentrations were significantly increased (+35%) after i.p. 5,7-DHT injections in contrast to reduction (-89%) after i.c. 5,7-DHT; 5-hydroxyindole acetic acid/5-hydroxytryptamine (5-HIAA/5-HT) ratios were decreased (-20%) with either route. These data suggest that brainstem 5-HT hyperinnervation following i.p. 5,7-DHT injection modifies the functional consequences of injury in abating the 5-HT syndrome, but does not result in complete recovery since shaking behavior is enhanced. Loss of presynaptically mediated autoregulation or receptor dysregulation may play a major role in behavioral supersensitivity induced by 5-HTP in rats with 5,7-DHT lesions. To the extent that the 5-HT syndrome is mediated by 5-HT1A receptors and shaking behavior by 5-HT2 sites, differential responses to injury of 5-HT1A and 5-HT2 receptors may contribute to these behavioral differences.
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PMID:Brainstem serotonergic hyperinnervation modifies behavioral supersensitivity to 5-hydroxytryptophan in the rat. 258 10

There have been few previous studies of the functional significance of 5,7-dihydroxytryptamine (5,7-DHT) lesions made in neonatal rats. To study the role of serotonin (5-HT) in recovery of function, rat pups and adult rats were injected intracisternally with 5,7-DHT or saline and challenged acutely with the 5-HT precursor 5-hydroxytryptophan (5-HTP) 4 weeks later as a test of behavioral supersensitivity. Compared to 5,7-DHT lesions in adults, neonatal lesions induced significantly greater 5-HT depletions in brainstem, but 5-HT depletions in other regions were not significantly different in the two groups. Rats with early 5,7-DHT lesions displayed supersensitive behavioral responses to 5-HTP, consisting of all the component myoclonic-serotonergic behaviors seen in rats with 5,7-DHT lesions made as adults. However, there was significantly less 5-HTP-evoked head weaving, truncal myoclonus and shaking behavior in rats treated with 5,7-DHT as neonates. Body weight was reduced both in rats with early and late 5,7-DHT lesions, but reduction persisted in rats with early lesions. These data indicate overall similarity with some differences between neurochemical and behavioral effects of early and late 5,7-DHT lesions made by the intracisternal route. They suggest that recovery mechanisms did not occur or failed to reverse the neurochemical or behavioral consequences of early 5,7-DHT lesions.
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PMID:Intracisternal 5,7-dihydroxytryptamine lesions in neonatal and adult rats: comparison of response to 5-hydroxytryptophan. 278 68

The effect of fluperlapine--a new nonclassical neuroleptic--on the central serotoninergic system was studied. Fluperlapine antagonizes the head-twitch response induced by 5-hydroxytryptophan in mice and rats (the ED50 values are 0.3 mg/kg ip and 0.89 mg/kg ip respectively), counteracts forepaw clonic convulsions and tremor induced by tryptamine in rats (ED50 = 9.0 mg/kg ip and 7.5 mg/kg ip respectively), and abolishes hyperthermia induced by fenfluramine. In the flexor reflex preparation in spinal rats fluperlapine depresses the reflex only when given in higher doses. The drug given in low doses abolishes the stimulation of the flexor reflex evoked by quipazine and LSD (serotonin agonists) but not by clonidine (noradrenaline agonist). Higher doses of fluperlapine antagonise also the stimulatory effect of clonidine. Our findings demonstrate that fluperlapine shows potent central antiserotonin activity.
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PMID:Central antiserotonin action of fluperlapine. 286 38

The effects of two beta 2-adrenoceptor agonists with different lipophilicities were studied on tremor induced by L-5-hydroxytryptophan (L-5-HTP) in pargyline- and carbidopa-pretreated rats. Tremor was recorded and analysed by an objective method based on accelerometry. Clenbuterol, a lipophilic beta 2-selective agonist, dose-dependently enhanced tremor intensity, whereas the hydrophilic beta 2-agonist terbutaline had no effect. The clenbuterol-induced enhancement of tremor was completely abolished by the beta 2-selective antagonist ICI 118,551 but unchanged by the beta 1-selective antagonist metoprolol. The results suggest that centrally located beta 2-adrenoceptors can mediate a modulation of 5-hydroxytryptamine-induced tremor in rats.
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PMID:Central beta-adrenoceptors can modulate 5-hydroxytryptamine-induced tremor in rats. 286 14

The effect of beta-adrenoceptor antagonists, varying in lipophilicity and receptor selectivity, were studied on tremor elicited by L-5-hydroxytryptophan (L-5-HTP) in rats pretreated with a peripherally acting decarboxylase inhibitor and a monoamine oxidase inhibitor, or by the directly acting 5-HT agonist 5-methoxy-N,N-dimethyltryptamine (5-MeODMT). Plasma levels of the beta-adrenoceptor antagonists were determined simultaneously. The non-selective lipophilic adrenoceptor antagonist propranolol was found to dose-dependently reduce tremor intensity, whereas the non-selective hydrophilic adrenoceptor antagonist sotalol had no effect, indicating a central site of action. Furthermore, beta 1-selective blockade with the adrenoceptor antagonist metoprolol had no effect on tremor intensity, whereas the beta 2-selective antagonist ICI 118,551 dose-dependently suppressed tremor intensity, suggesting that the beta-adrenoceptor subtype involved is of the beta 2-type. These results suggest that blockade of centrally located beta 2-adrenoceptors are able to attenuate the tremor response following 5-hydroxytryptamine receptor activation.
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PMID:Blockade of central beta-adrenoceptors attenuates tremor induced by 5-hydroxytryptamine (5-HT)-receptor activation in rats. 288 12


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