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S Bischoff

Publications and source records attributed to S Bischoff.

At least 55 records · Page 3Linked to original sources
PubMed1988

The neurotensin analog xenopsin excites nigral dopamine neurons.

The electrophysiological effects of neurotensin (NT), its analog xenopsin, and the fragment NT-(1-8) on the activity of dopaminergic neurons in rat substantia nigra slices were compared. Xenopsin and NT produced a concentration-dependent increase in the firing rate. The mean firing rate was increased by 58.5% with xenopsin (0.1 microM) and 49.1% with NT (0.1 microM). NT-(1-8) was inactive at this concentration. Dopamine (100 microM) inhibited firing in these neurons by 54.7%. These data provide evidence that xenopsin mimics the physiological effects of NT.

Action Potentials↗
PubMed1988

Interactions of isamoltane (CGP 361A), an anxiolytic phenoxypropanolamine derivative, with 5-HT1 receptor subtypes in the rat brain.

Isamoltane (CGP 361A; (1-(2-(1-pyrrolyl)-phenoxy)-3-isopropylamino-2-propanol hydrochloride), a beta-adrenoceptor ligand (IC50 = 8.4 nmol/l) which has reported activity as an anxiolytic in man was found to be a reasonably active inhibitor of the binding of [125I]ICYP to 5-HT1B recognition sites in rat brain membranes with 27-fold selectivity (IC50 = 39 nmol/l) as compared to the inhibition of binding of [3H]8-OH-DPAT to 5-HT1A receptors (IC50 = 1070 nmol/l). This selectivity was considerably greater than that observed for other beta-adrenoceptor ligands including propranolol (5-HT1A/5-HT1B ratio = 2), oxpenolol (3.5) and cyanopindolol (8.7). The 5-HT1B activity of the compound resided in the (-)-enantiomer. (-)-Isamoltane had weak activity (IC50 3-10 mumol/l) at 5-HT2 and alpha 1-adrenoceptors. The compound was devoid of activity at a number of other central neurotransmitter recognition sites including the 5-HT1C site. Isamoltane increased the electrically evoked release of [3H]5-HT from prelabeled rat cortical slices in a manner similar to that of cyanopindolol. While both compounds were similar in potency to methiothepin, they had lower efficacy. Oxprenolol was less potent that both isamoltane and cyanopindolol while propranolol was essentially inactive. The effects of the compounds on 5-HT release appeared to be correlated with their 5-HT1B rather than 5-HT1A activity. In vivo, isamoltane increased 5-HTP accumulation in rat cortex following central decarboxylase inhibition at doses of 1 and 3 mg/kg i.p. At higher doses this effect was gradually diminished. Similar, but less clearcut results were obtained with cyanopindolol and oxprenolol, but propranolol was ineffective. No changes in brain tryptophan levels were associated with the isamoltane-evoked changes in brain 5-HTP levels. In reserpinized animals, isamoltane reduced 5-HTP accumulation even at doses which enhanced accumulation of this metabolite when given alone. The effects of the putative 5-HT1B agonist, m-trifluoromethylphenylpiperazine (TFMPP), the mixed 5-HT autoreceptor agonist/antagonist/beta-adrenoceptor antagonist, pindolol, the 5-HT uptake inhibitor, CGP 6085A and the MAO-A inhibitor, brofaromine, were not antagonized by pretreatment with isamoltane. The possibility that isamoltane and the other beta-adrenoceptor antagonists are antagonists at 5-HT1B receptors and that their effect on 5-HT synthesis in vivo is the net result of their agonist/antagonist effects at 5-HT1A and 5-HT1B receptors is discussed in relation to the potential mechanism of the anxiolytic activity of isamoltane.

5-Hydroxytryptophan↗
PubMed1988

Blockade of hippocampal dopamine (DA) receptors: a tool for antipsychotics with low extrapyramidal side effects.

1. 32 neuroleptics (NL) and a Ciba-Geigy antipsychotic (savoxepine, CGP 19 486 A) were tested on adult male rats and mice. 2. Interaction with D2 DA receptors was assessed using in vivo (3H)spiperone (SPI) binding in rat hippocampus and striatum. 3. Antipsychotic efficacy of NL was checked by their ability to antagonize apomorphine-induced climbing behavior in mice. 4. We found a good correlation between blockade of DA receptors in hippocampus and antagonism of climbing with both classical and atypical NL. 5. No correlation was found between blockade of DA receptors in striatum and climbing with the atypical NL. 6. It is suggested that NL exerting preferential blockade of hippocampal as compared to striatal DA receptors may show a better dissociation between antipsychotic efficacy and induction of extrapyramidal side effects (EPS) in the clinic. The antipsychotic agent savoxepine, displayed such a favourable profile of action.

Animals↗
PubMed1988

Interaction of the D1 receptor antagonist SCH 23390 with the central 5-HT system: radioligand binding studies, measurements of biochemical parameters and effects on L-5-HTP syndrome.

The interaction of SCH 23390 with dopamine (DA) and serotonin (5-HT) systems has been examined in vivo and in vitro. Like selective 5-HT2 blockers, SCH 23390 inhibited in vivo [3H]spiperone binding in the rat frontal cortex (ID50: 1.5 mg/kg) without interacting at D2 sites. SCH 23390 was equipotent to cinanserin and methysergide. In vitro, SCH 23390 inhibited [3H]ketanserin binding to 5-HT2 sites (IC50 = 30 nM). Biochemical parameters linked to DA and 5-HT were not changed excepted in striatum where SCH 23390 increased HVA and DOPAC. In the L-5-HTP syndrome model, SCH 23390 clearly showed antagonism of 5-HT2 receptors. SCH 23390 had weak affinity for 5-HT1B (IC50 = 0.5 microM), 5-HT1A (IC50 = 2.6 microM) and alpha 1-adrenergic receptors (IC50 = 4.4 microM).

5-Hydroxytryptophan↗
PubMed1986

Detection of dopamine receptors in homogenates of rat hippocampus and other brain areas.

The binding of [3H]spiperone (24-26 pM) specifically to the dopaminergic (DAergic) D2 site has been investigated in homogenates of rat hippocampus, pineal gland and cerebellum. It was found that specific binding in hippocampal homogenates was heat-labile and for a part pH-sensitive. Like striatal tissue, binding to the dopaminergic D2 site in hippocampal and cerebellar homogenates was greatly reduced by (pre)incubation with the iron chelator o-phenanthroline. The binding characteristics in hippocampus and cerebellum have been compared to those in the striatum. In all tissues tested, low (74-138 times fewer than in striatum) but significant numbers of DAergic D2 sites were found. The DAergic D2 site in the hippocampus, as far as measured in cerebellum and pineal gland exhibited similar binding characteristics to that in the striatum.

Animals↗
PubMed1986

Ifoxetine, a compound with atypical effects on serotonin uptake.

Ifoxetine (CGP 15210 G; (+/-)-bis-[cis-3-hydroxy-4-(2,3-dimethyl-phenoxy)]-piperidine sulfate) prevented the depletion of serotonin (5-HT) induced by H 75/12 and p-chloromethamphetamine in the rat brain, and that caused by endogenously released dopamine after the combined administration of haloperidol and amfonelic acid in the rat striatum. These effects are typically caused by compounds that inhibit 5-HT reuptake. Unexpectedly, ifoxetine only weakly inhibited the uptake of radiolabelled 5-HT into rat brain synaptosomes in vitro or ex vivo, the human thrombocytes in vitro or into rat thrombocytes after pretreatment. The following, among the possible explanations for this apparent discrepancy, were considered and regarded as unlikely: the involvement of an active metabolite; the possibility that ifoxetine accumulates in the brain to an extent sufficient to cause in vivo uptake inhibition; a pharmacokinetic interaction with the depleting agents. The possibility that the depletor tests give false positives was also considered. However, ifoxetine lowered brain 5-hydroxyindoleacetic acid and reduced the accumulation of 5-hydroxytryptophan after central decarboxylase inhibition. This suggests that it also interferes with 5-HT metabolism in the absence of depleting agents, which means that it interacts in some way with serotonergic transmission. Ifoxetine displayed weak or no interactions with 5-HT1, 5-HT2, alpha 1-, alpha 2- and beta-noradrenoceptors, histamine H1, muscarinic acetylcholine, opiate, GABA A, and benzodiazepine receptors in vitro, and with dopamine and 5-HT2 receptors in vivo. It did not antagonize the noradrenaline (NA) depletion induced by H 77/77 in rat brain and only weakly interfered with the uptake of i.v. injected radiolabelled NA into the rat heart. This suggests that its interaction with the 5-HT system is specific. Due to its atypical properties, among which the rather weak potentiation of the neurological effects of 5-hydroxytryptophan is also important, ifoxetine may exhibit a therapeutic and/or side-effect profile which differs from that of classical 5-HT uptake inhibitors.

Animals↗
PubMed1986

The D-1 dopamine receptor antagonist SCH 23390 also interacts potently with brain serotonin (5-HT2) receptors.

The interaction of SCH 23390 with central serotonin 5-HT2 receptors was studied in vivo on [3H]spiperone binding and in vitro on [3H]ketanserin binding. SCH 23390 inhibited [3H]spiperone binding in rat frontal cortex with an ID50 of 1.5 mg/kg i.p., thus being equipotent to the two 5-HT2 antagonists cinanserin and methysergide. In vitro, SCH 23390 competed with [3H]ketanserin with an IC50 of 30 nM. These data indicate that SCH 23390 also binds with high affinity to 5-HT2 receptors in rat brain.

Animals↗
PubMed1984

Affinity changes of rat striatal dopamine receptors in vivo after acute bupropion treatment.

The effect of bupropion (Wellbutrin) was studied on in vivo [3H]spiperone binding in rat striatum and cerebellum. The compound increased binding dose dependently in striatum whereas no effect was observed in cerebellum. Saturation analyses of in vivo binding in the striatum revealed an increased affinity of the receptors rather than changes in the number of binding sites. These results are the first demonstration of an increased sensitivity of central dopamine receptors after acute bupropion treatment.

Animals↗
PubMed1982

Septo-hippocampal system: target for substituted benzamides.

Effects of the substituted benzamide, and of oxiperomide on DA receptors and on Da-related behaviors were the object of the study. The benzamides were practically inactive on DA-sensitive adenylate cyclase and on in vitro [3H] spiperone binding (in the absence of sodium ions). However, all of them inhibited in vivo [3H] spiperone binding in various rat brain regions; this in vivo effect was especially apparent in hippocampus and septum. In frontal cortex, the benzamides (with the exception of metoclopramide) produced only a partial inhibition of [3H] spiperone binding. Such inhibition also occurred in the striatum with sulpiride and tiapride. The results suggest that substituted benzamides are DA antagonists due to their ability to inhibit in vivo [3H] spiperone binding. The lack of agreement between in vivo and in vitro tests is also discussed.

Adenylyl Cyclases↗
PubMed1982

Correlations between different measures of antiserotonin activity of drugs. Study with neuroleptics and serotonin receptor blockers.

The antiserotonin properties of a series of neuroleptics, 5-HT-receptor blockers and some adrenoceptor antagonists were investigated in several in vivo test systems (L-5-HTP syndrome and 5-HT-paw edema in the rat) and in an in vitro test (isolated rat uterus preparation). The results were compared to the results obtained with these drugs in an in vivo 3H-spiperone binding assay in the rat. The computations of the relative ED50 (or IC50) values obtained in different test procedures showed that the ability of drugs to bind to 5-HT receptors labelled by 3H-spiperone in the rat frontal cortex correlates fairly well with their potencies to inhibit the L-5-HTP syndrome or 5-HT-induced rat pawedema (Spearman rank correlation coefficient, r = 0.80 and 0.79 respectively, n = 22). In an in vitro test (rat uterus) the estimated 5-HT-receptor blocking potency of the tested drugs did not, however, correlate with any of the in vivo measures used for this purpose. The results suggest, therefore, that for the determination of central antiserotonin effects of drugs in the rat, functional in vivo tests (L-5-HTP syndrome or 5-HT-induced rat paw-edema) could yield about the same information as the specific, in vivo 3H-spiperone binding assay. The 5-HT-receptor type mediating the behavioral responses to L-5-HTP is tentatively defined as a 5-HT2 receptor.

5-Hydroxytryptophan↗
PubMed1980

In vivo [3H]spiperone binding to the rat hippocampal formation: involvement of dopamine receptors.

The existence of DA receptors in the rat hippocampus was demonstrated with an in vivo [3H]spiperone radioreceptor assay. Kinetic studies revealed that maximum binding of [3H]spiperone in hippocampus was much smaller than in striatum and frontal cortex but much higher than in cerebellum. In inhibition studies of [3H]spiperone binding, all neuroleptics tested were active in hippocampus as well as in striatum. In contrast, 5HT antagonists were definitely less potent in these two brain regions than in frontal cortex. Finally, even when 5HT receptors were blocked, dipropyl-ATN and haloperidol remained fully effective in hippocampus, striatum, but also in frontal cortex although to a lesser degree. From these results it was concluded that [3H]spiperone binds mainly to DA receptors in hippocampus as well as in striatum, whereas both 5HT and DA receptors are present in frontal cortex.

Animals↗
PubMed1980

[Parameters of contentment in old age].

In an interview study of 480 aged persons, questions on satisfaction with several aspects of life were included. A factor analysis allows to distinguish a factor relating to "depressivity" from a factor "satisfaction with social contacts" and a health-related dimension.

Aged↗
PubMed1980

Origin of dopaminergic innervation of the rat hippocampal formation.

The origin of the dopaminergic afferents to the rat hippocampal formation has been investigated by measuring dopamine and DOPAC contents in this area after electrolytic or chemical lesion of the ventral tegmental area (A10) or substantia nigra (A9). The present study indicates that dopaminergic afferents to the hippocampal formation originate from the A10 and A9 dopaminergic cell groups. The 'anterior' hippocampal formation receives a major input from the A10 area whereas the 'posterior' hippocampal region receives dopaminergic afferents from both A9 and A10 cell groups. The dopaminergic afferents are entering the hippocampal region mainly through the dorsal route.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1979

Dopamine metabolism, spiperone binding and adenylate cyclase activity in the adult rat hippocampus after ingrowth of dopaminergic neurones from embryonic implants.

The growth of dopamine (DA) neurones of rat embryonic mesencephalic brain tissue implanted close to the anterior part of the hippocampus of adult rats was studied by measuring the levels of DA and 3,4-dihydroxyphenylacetic acid (DOPAC) in the host hippocampus. The hippocampal levels of DA and DOPAC reached maximal values 6 months after transplantation. The neuroleptic drug haloperidol evoked an increase in the levels of DOPAC. No evidence was found for the induction of DA-sensitive adenylate cyclase activity or of binding sites of [3H]spiperone. These results indicate that there is a substantial ingrowth of transplanted DA neurones into the host hippocampus, but no evidence was found for the development of functional contacts between the embryonic DA neurons and the host tissue.

3,4-Dihydroxyphenylacetic Acid↗