benzofurans and 4-(5-6-dimethyl-2-benzofuranyl)piperidine

The sensitivity of rostral and cingulate cortical neurons to microiontophoretically administered serotonin (5-HT) was compared in groups of rats treated either acutely or chronically for different periods with various drugs. The drugs used were: desipramine (10 mg/kg), clomipramine (10 mg/kg), CGP 6085 (10 mg/kg), clorgyline (0.3 mg/kg), and deprenyl (1 mg/kg). Serotonin and, in some instances, gamma-aminobutyric acid (GABA) were applied microiontophoretically over periods of 60 sec with various ejection currents to spontaneously active neurons in the rostral and cingulate cortex. Of all the compounds tested, only clorgyline produced a marked desensitization to 5-HT in both cortical areas. After prolonged treatment with all the other drugs, no change in the sensitivity to serotonin was observed. The desensitization to 5-HT induced by clorgyline developed after 4 to 10 days of treatment. The responsiveness of these cells to GABA was unchanged after chronic exposure to clorgyline. The present results are consistent with those biochemical studies showing that chronic treatment with 5-HT-uptake-blocking compounds has no effect on 5-HT-binding characteristics, as well as with the observation that prolonged treatment with the monoamine-oxidase A-type blocker clorgyline reduces the number of 5-HT-binding sites.

Topics: Animals; Benzofurans; Cerebral Cortex; Clomipramine; Clorgyline; Desipramine; Electric Conductivity; gamma-Aminobutyric Acid; Male; Monoamine Oxidase Inhibitors; Neurons; Piperidines; Rats; Selegiline; Serotonin; Serotonin Antagonists

Potentiation of the effect of haloperidol on dopamine metabolism by the 5-HT uptake inhibitor CGP 6085 A, and antagonism of this effect by the 5-HT antagonist mianserin were observed in the mesolimbic area and the frontal cortex of the rat brain. A similar effect was reported earlier in the corpus striatum. This suggests that serotoninergic modulation of dopamine neurons is a generally-occurring phenomenon in the brain.

Topics: 3,4-Dihydroxyphenylacetic Acid; Animals; Benzofurans; Cerebral Cortex; Corpus Striatum; Dopamine; Fenclonine; Haloperidol; Homovanillic Acid; Limbic System; Mianserin; Neurons; Organ Specificity; Piperidines; Rats; Serotonin

Topics: Aggression; Animals; Benzofurans; Brain; Electric Stimulation; Humans; Male; Mesencephalon; Mice; Piperidines; Quipazine; Raphe Nuclei; Rats; Receptors, Serotonin; Serotonin

Topics: Animals; Benzofurans; Blood Platelets; Brain; Dopamine; Humans; Hydroxyindoleacetic Acid; In Vitro Techniques; Liver; Monoamine Oxidase; Myocardium; Norepinephrine; Piperidines; Rats; Serotonin; Serotonin Antagonists; Synaptosomes; Time Factors

The potentiation of the effect of haloperidol on rat striatal homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC) by a serotonin (5-HT) uptake inhibitor, CGP 6085 A, has been further investigated. The evidence that this effect of CGP 6085 A is related to its 5-HT uptake inhibitory properties is discussed. The potentiation was antagonized by scopolamine and baclofen, and disappeared more rapidly than the uptake inhibitory effects of CGP 6085 A, presumably because the effects of uptake inhibition were counteracted by a reduction in 5-HT synthesis. CGP 6085 A also potentiated the effects of fluphenazine and pimozide, but not those of a number of other neuroleptics. It also failed to restore the effect of haloperidol in animals treated chronically with the neuroleptic. These results appear to indicate that CGP 6085 A can only stimulate DA neurons if their activity is already above the resting level. The antagonism of this effect by scopolamine suggests that the site of action of the 5-HT uptake inhibitor is before a cholinergic neuron.

Topics: 3,4-Dihydroxyphenylacetic Acid; Animals; Baclofen; Benzofurans; Corpus Striatum; Dopamine; Female; Haloperidol; Homovanillic Acid; Piperidines; Rats; Scopolamine; Serotonin Antagonists; Time Factors

The effects of two new compounds, 1-(1-methylamino-2-hydroxy-3-propyl)-dibenzo[b,e]bicyclo[2,2,2]octadiene-HCl (C 49802-B-Ba) and 4-(5,6-dimethyl-2-benzofuranyl) piperidine HCl (CGP 6085 A), on noradrenaline (NA) and serotonin (5-HT) uptake were investigated in different test systems, CGP 6085 A is a very potent and selective inhibitor of 5-HT uptake in rat brain (ED50 1-4 mg/kg p.o., depending on test system). Doses up to 1000 mg/kg p.o. did not inhibit NA uptake. C 49802-B-Ba is a potent and selective inhibitor of NA uptake in rat brain (ED50 5-10 mg/kg p.o. depending on test system) and heart (ED50 1.5 mg/kg p.o.). At 300 mg/kg p.o., this compound caused no inhibition of 5-HT uptake.

Topics: Animals; Benzofurans; Brain; Bridged Bicyclo Compounds; Bridged-Ring Compounds; Depression, Chemical; Female; In Vitro Techniques; Myocardium; Norepinephrine; Piperidines; Rats; Serotonin