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 11,717 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. On the basis of both in vitro and in vivo experiments fluvoxamine has been characterized as a potential anti-depressant drug with almost exclusively 5-hydroxytryptamine (5-HT) uptake inhibiting properties. 2. Fluvoxamine is effective in inhibiting 5-ht uptake by blood platelets and brain synaptosomes. Due to inhibition of the membrane pump the compound prevents 5-HT depletion by the tyramine-derivatives H 75/12 and H 77/77. As a result of the interference with the neuronal re-uptake mechanism for 5-HT, fluvoxamine produces a decreased 5-HT turnover in the brain. Effects of 5-hydroxytryptophan (5-HTP) are potentiated in mice and in combination with pargyline, fluvoxamine induces 5-HT-like behavioural effects. 3. In contrast to tricyclic antidepressants, noradrenaline uptake processes are either unaffected or only slightly inhibited by fluvoxamine. The noradrenaline depleting effects of tyramine derivates are not influenced by fluvoxamine. Reserpine effects, such as ptosis are affected only at very high doses of the test compound. The antagonism by fluvoxamine of the reserpine-induced lowering of the pentamethylenetetrazole convulsive threshold can be regarded as due to an effect upon 5-HT uptake. In contrast to the effects of desmethylimipramine and imipramine, no stimulatory effects are found in rats when rapidly acting reserpine-like compounds are given following a dose of fluvoxamine.
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PMID:Fluvoxamine, a specific 5-hydroxytryptamine uptake inhibitor. 30 26

The effects of viloxazine, a clinically effective antidepressant, on noradrenaline (NA) and 5-hydroxytryptamine (5-HT) uptake and various related pharmacological activities were determined and compared to those of the tricyclic antidepressants desimipramine, imipramine, and amitriptyline. Viloxazine inhibitied [3H]NA uptake in the mouse and rat heart, being maximally about one half as potent as imipramine with a similar onset, but shorter duration of action than imipramine. The drug did not inhibit [3H]NA uptake in rat medulla or hypothalamus in contrast to desimipramine and imipramine, but it did alter [3H]NA metabolites in a similar manner. Viloxazine, like desimipramine, was a weak blocker of mouse brain 5-HT uptake, but differed from desimipramine as it poteniated 5-HT-mediated functions in the mouse and rat, as did imipramine and amitriptyline, the latter drugs being relatively potent blockers of 5-HT uptake. Viloxazine potentiated the L-DOPA behavioural syndrome in the mouse, antagonized reserpine-induced ptosis and hypothermia in the mouse, and inhibited gastric acid secretion in the rat, but was less potent than the tricyclic antidepressants. No appreciable in vivo inhibition of monoamine oxidase (EC 1.4.3.4.) activity in the mouse was exhibited. Like imipramine, the drug potentiated the ocular effects of L-adrenaline in the rabbit. It was similar to imipramine in potency in potentiating the apomorphine-induced gnawing in the mouse. The drug antagonized oxotremorine-induced hypothermia in the mouse but differed from the tricyclic antidepressants in not exhibiting the anticholinergic effects of blocking the tremors, salivation and lacrimation. Thus, viloxazine exhibits activities related to the biogenic amines both similar to and different from the tricyclics desimipramine, imipramine, and amitriptyline. These actions appear to be of relevance with respect to the antidepressant action of this drug.
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PMID:Effects of viloxazine, an antidepressant agent, on biogenic amine uptake mechanisms and related activities. 97 78

One hour after the intraperitoneal (i.p.) injection of FMH (200 mg/kg), locomotor activity and rearing were statistically reduced, by 3 hours later, only the locomotor activity was reduced in rats. The i.p. injection of FMH (100 and 200 mg/kg) had no effects on motor incoordination, blood pressure, heart rate and tetrabenazine-induced ptosis in rats. One and 3 hours after FMH injection, the histamine levels significantly decreased in the hypothalamus, cortex and thalamus, slightly in the olfactory bulb, amygdala, pons-medulla oblongata and midbrain, but very little in the striatum, hippocampus, cerebellum and pituitary. On the other hand, noradrenaline and dopamine levels were not affected in most of the regional parts, although in the cortex and midbrain, the dopamine levels were slightly reduced 1 hour after FMH (100 and 200 mg/kg). These data showed that central histamine may play an important role in the locomotor activity of rats.
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PMID:Effects of alpha-fluoromethylhistidine on locomotor activity, brain histamine and catecholamine contents in rats. 159 29

The study aimed at evaluating a possible relationship between the adrenergic system tone determined with the excretion of catecholamines with the urine and an incidence of the ventricular arrhythmias in patients with the mitral valve prolapse. The study included 20 patients (13 women and 7 men aged between 20 and 50 years; mean = 31.6 years) with the mitral valve prolapse syndrome diagnosed with the aid of the patients' history, physical examinations and echocardiography. Echocardiograms have shown anterior mitral leaflet prolapse in 7 patients, posterior mitral leaflet prolapse in 8 patients, and both mitral leaflets prolapse in the remaining 5 patients. Daily excretion of adrenaline and noradrenaline was measured with Van Euler and Lishajko's fluorimetric technique. Cardiac arrhythmias were determined with a 24-hour ECG monitoring and classified according to Lown. Premature ventricular contractions of class I were seen in 1 patient, of class II in 5, class III in 1, class IV in 2, and class V in 3 patients. Holter monitoring technique did not show the arrhythmias in 8 patients. Daily adrenaline and noradrenaline excretion with the urine was within the normal values (3.2-30.8 ug and 0.2-16.2 ug, respectively) in all examined patients. Daily urine noradrenaline was higher in patients with serious ventricular arrhythmias (Lown's class V) than mean values in the whole examined group.
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PMID:[Arrhythmia in patients with mitral valve prolapse syndrome and the status of the sympathetic nervous system]. 169 13

Behavioural effects on dopaminergic transmission of a phenylindane derivative, Lu 19-005 [(+/-)-trans-3-(3,4-dichlorophenyl)-N-methyl-l-indanamine, HCI], with potent inhibitory effect on dopamine (DA), noradrenaline (NA) and serotonin (5-HT) uptake in rats and the effect on DA, NA and 5-HT activity in mice have been studied and compared with those of other known DA, NA and 5-HT uptake inhibitors with different selectivity ratios. Lu 19-005 induced stereotyped behaviour after parenteral and oral administration with a duration of action of more than 24 h. The stereotyped licking and biting induced by Lu 19-005 was antagonized by reserpine and cis(Z)-flupentixol, but not affected by prazosin, p-chlorophenylalanine and alpha-methyl-p-tyrosine pretreatments. Metergoline slightly facilitated the onset of stereotypy. Lower doses of Lu 19-005 induced ipsilateral circling in unilaterally 6-hydroxy-DA-lesioned rats. Finally, Lu 19-005 antagonized the catalepsy induced by perphenazine. In mice, Lu 19-005 potentiated the apomorphine-induced gnawing, reversed tetrabenazine-induced ptosis and potentiated the behavioural effects of 5-HTP within a similar dose range. The effects of Lu 19-005 were compared with those of other reference compounds. Nomifensine had qualitatively similar effects in rats although of much shorter duration. In mice, nomifensine selectively reversed tetrabenazine-induced ptosis. Weaker effects in all test models were found with bupropion, LR 5182 and GBR 13.069, compounds with inhibitory effect on DA and NA uptake. The DA-, NA- and 5-HT-uptake inhibitor diclofensine, however, had no effect in rats except in the 6-hydroxy-DA-circling test and had low potency in mice. The specific 5-HT- and NA-uptake inhibitors citalopram and talsupram, respectively, were ineffective in all rat models.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pharmacology in vivo of the phenylindan derivative, Lu 19-005, a new potent inhibitor of dopamine, noradrenaline and 5-hydroxytryptamine uptake in rat brain. 240 54

Fluperlapine was compared with clozapine, chlorpromazine, haloperidol and imipramine regarding its effects on some cholinergic and noradrenergic animal systems. Fluperlapine and clozapine showed the most pronounced anticholinergic effects. Fluperlapine was equipotent with clozapine in displacing [3H]-QNB from muscarinic receptors of the calf cerebral cortex (IC50 about 15 nM). In the mydriasis test in the mouse and in the crayfish hindgut bioassay the differences between fluperlapine and clozapine were small. Like the other antischizophrenic drugs tested, fluperlapine displayed a marked affinity for alpha 1-adrenoceptors (calf cerebral cortex: IC50 about 10 nM) but a negligible affinity for alpha 2-adrenoceptors in the same tissue. Only clozapine showed a weak affinity for the latter receptor type. Fluperlapine was as effective as imipramine in antagonizing tetrabenazine-induced ptosis in the rat, the anti-ptotic effect remaining constant after up to ten daily drug administrations. Still, imipramine was stronger than fluperlapine as an inhibitor of the accumulation of [3H]-noradrenaline ([3H]-NA) in rat cerebral cortex slices. Fluperlapine's effects on the spontaneous and the electrically-induced release of [3H]-NA from rat cerebral cortex slices, with and without protriptyline, showed it to be an inhibitor of the reuptake of NA. The results indicate that the pharmacological profile of fluperlapine is similar to that of clozapine, with additional antidepressant properties.
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PMID:Biochemical and pharmacological effects of fluperlapine on noradrenaline and acetylcholine systems in some rodent, bovine and crustacean preparations. 287 2

A woman was referred with severe orthostatic hypotension at the age of 21. Ptosis, skeletal muscle hypotonia, and recurrent hypoglycaemia had been noticed in early childhood. There was noradrenergic denervation and adrenomedullary failure but baroreflex afferents, cholinergic innervation, and adrenocortical function were intact. Noradrenaline and adrenaline were undetectable in plasma, urine, and cerebrospinal fluid (CSF), but dopamine was 7-fold to 12-fold normal in plasma, 4-fold normal in urine, and 20-fold normal in CSF. Measurements of catecholamine metabolites showed further evidence for impairment of noradrenaline and adrenaline biosynthesis due to deficient dopamine-beta-hydroxylation. Dopamine-beta-hydroxylase was undetectable in plasma and CSF. Physiological and pharmacological stimuli of sympathetic neurotransmitter release caused increases in plasma dopamine rather than plasma noradrenaline.
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PMID:Congenital dopamine-beta-hydroxylase deficiency. A novel orthostatic syndrome. 288 16

Chronic administration of guanethidine to adult rats induces a selective autoimmune adrenergic neuropathy. Physiological and biochemical features of this disorder in the peripheral nervous system were explored in young adult Sprague-Dawley rats given daily intraperitoneal guanethidine monosulfate for 5 weeks. Control rats received daily saline injections. The guanethidine-treated animals gained less weight, had ptosis, and had a lower mean arterial blood pressure in the supine and upright tilted positions. Norepinephrine was depleted in the peroneal, sural, tibial, and vagal nerves, the nutrient artery to the tibial nerve and in the superior cervical sympathetic ganglion of the drug-treated animals. On light microscopy, there was an inflammatory cell infiltrate and neuron loss in the superior cervical ganglion. Caudal and sciatic-tibial nerve conduction values were well preserved in the guanethidine-treated animals as was the 'C' potential derived from unmyelinated vagal fibers recorded in an in vitro chamber. The 'C' potential recorded from the cervical sympathetic trunk, however, was reduced in amplitude correlating with the loss of norepinephrine content in the harvested contralateral superior cervical sympathetic ganglion. The findings further support the view that guanethidine produces a selective adrenergic neuropathy in the rat--providing a useful standard with which to gauge autonomic involvement in other models of neuropathy. In addition, loss of the cervical sympathetic 'C' potential suggests that this presumed preganglionic structure also contains postganglionic adrenergic fibers.
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PMID:Guanethidine adrenergic neuropathy: an animal model of selective autonomic neuropathy. 322 70

The central action of 2,3,3a,4,5,6-hexahydro-8-methyl-1H-pyrazino[3,2,1-j,k]carbazole hydrochloride (pirlindole, PIR) in mice and rats was studied. PIR inhibited the 3H-5-hydroxytryptamine (5-HT) uptake in the rat cerebral cortex, not affecting the uptake of 3H-noradrenaline. PIR counteracted the reserpine ptosis but did not alter the apomorphine hypothermia. It enhanced the L-dopa effect on the locomotor activity and the L-5-hydroxytryptophan (L-5-HTP)-induced head twitch reaction in mice. PIR also facilitated the effect of L-dopa and L-5-HTP on the hind limb flexor reflex of the spinal rat. The clonidine sedation (but not hypothermia) was attenuated by PIR. PIR given repeatedly for 18 days increased the binding of 3H-prazosin in the brain cortex (decreasing the KD value), but did not affect the binding of 3H-dihydroalprenolol. The obtained results indicate that PIR inhibits the 5-HT uptake, displays characteristics of a monoamineoxidase inhibitor and, when given repeatedly, increases the binding to alpha 1-adrenoceptors in the cerebral cortex.
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PMID:Central action of the antidepressant drug pirlindole. 349 Aug 54

The pharmacological properties of MO-8282 (1,2,3,4-tetrahydro-2-methyl-9H-dibenzo [3,4: 6,7]cyclohepta [1,2-c]pyridine maleate) as an antidepressant were investigated. At doses 10 times less than those of amitriptyline, MO-8282 showed similar potencies in reducing the duration of immobility during forced swimming in rats and in potentiating stereotype induced by L-DOPA. Intermediate doses of MO-8282 reduced the duration of immobility during forced swimming, in mice as well, suppressed muricide behavior of olfactory-bulbectomized rats and antagonized clonidine-induced suppression of exploratory activity in mice. MO-8282 moderately antagonized the ptosis but not the hypothermia induced by reserpine in mice. MO-8282 exhibited weak antagonism against the tremor, lacrimation and diarrhea induced by tremorine, but its activity was milder than that of amitriptyline. The uptake of noradrenaline into rat hypothalamic synaptosomes was inhibited by MO-8282 at concentrations 20 times less than equally effective doses of amitriptyline, but the uptake of dopamine or serotonin was unaffected by MO-8282. A single oral administration of MO-8282 at a dose of 30 mg/kg accelerated noradrenaline turnover, but did not affect dopamine and serotonin turnover in the rat brain. MO-8282 strongly inhibited noradrenaline-, histamine- or adenosine-sensitive adenylate cyclase activity of guinea pig brain. Its mode of action differed from that of imipramine, rather resembling that of mianserin. MO-8282 did not affect monoamine oxidase activity of rat liver. These results suggest that the pharmacological characteristics of MO-8282 are different from those of tricyclic antidepressants and rather similar to those of mianserin, but more potent. The results, therefore, indicate that MO-8282 is possibly a novel antidepressant.
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PMID:[Pharmacological properties of MO-8282, a novel antidepressant]. 379 61


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