Biomedical subjects

R Steinberg

Publications and source records attributed to R Steinberg.

At least 55 records · Page 3Linked to original sources

PubMed1995

SR 48692-sensitive neurotensin receptors modulate acetylcholine release in the rat striatum.

The effects of stimulation and blockade of neurotensin receptors on striatal acetylcholine release were examined in anaesthetized rats using microdialysis. Local perfusion with neurotensin (100 nM) did not influence the release of acetylcholine. Application of neurotensin (100 nM) 30 min after haloperidol (125 micrograms/kg, i.p.) increased acetylcholine levels to 188% compared to 120% when haloperidol was administered alone. SR 48692 (3-100 micrograms/kg, i.p.) dose-dependently reduced the stimulatory effect of neurotensin in the presence of haloperidol. Comparable antagonism was observed with SR 48527, a chemically-related compound with high affinity for neurotensin receptors, but not with SR 49711, its low-affinity antipode. These results indicate that high affinity neurotensin receptors regulate acetylcholine release, when D2-dopaminergic inhibitory input is suppressed.

Acetylcholine↗

PubMed1995

Neurochemical and behavioural effects of neurotensin vs [D-Tyr11]neurotensin on mesolimbic dopaminergic function.

Microinjection of neurotensin(1-13) or neurotensin(8-13) into the ventral tegmental area (VTA) of anaesthetized rats produced dose-dependent (1-100 pg) dopamine release in the nucleus accumbens as measured by differential pulse amperometry (DPA). Higher doses (100 pg-10 ng) of [D-Tyr11]neurotensin were required to produce an identical effect. In addition, the 3 peptides enhanced the K(+)-evoked [3H]DA release from nucleus accumbens slices. The stimulatory actions produced by 10(-8) M neurotensin(1-13) and neurotensin(8-13) were respectively of 96% and 72% while the effect of [D-Tyr11]neurotensin was only of 79% at 10(-6) M. Unilateral application of the 3 peptides in the VTA of cannulated rats produced contralateral circling. [D-Tyr11]neurotensin was effective in a dose-dependent manner, between 40 and 320 ng. Similar effects were observed with 80 ng of neurotensin(1-13) and neurotensin(8-13) in presence of the protease inhibitor thiorphan. In view of the higher potency of neurotensin(1-13) and neurotensin(8-13) versus [D-Tyr11]neurotensin to stimulate DA release both in vivo and in vitro and the higher efficacy of [D-Tyr11]neurotensin to induce circling, this study further strengthens the concept of neurotensin receptor heterogeneity.

Animals↗

PubMed1995

Blockade of neurotensin receptor by SR 48692 potentiates the facilitatory effect of haloperidol on the evoked in vivo dopamine release in the rat nucleus accumbens.

The present experiments assessed the effects of SR 48692, a selective nonpeptide antagonist of neurotensin receptors, on mesolimbic dopaminergic neurotransmission. Dopamine release evoked by the electrical stimulation of the median forebrain bundle (20 Hz, 10 s) was measured in the nucleus accumbens of urethane-anesthetized rats using differential pulse amperometry combined with carbon fiber electrodes. SR 48692 (0.1 mg/kg, i.p.) alone did not affect this release, whereas it dose-dependently (0.03-1 mg/kg, i.p.) enhanced the haloperidol (50 micrograms/kg, i.p.)-induced facilitation of the electrically evoked DA release. The increase induced by haloperidol (92 +/- 26% above control values 30 min after injection) was potentiated by SR 48692 (264 +/- 75% at 0.03 mg/kg, 428 +/- 113% at 0.1 mg/kg, and 480 +/- 135% at 1 mg/kg). Effects identical to those of SR 48692 were obtained with SR 48527, a chemically related compound with a high affinity for neurotensin receptors, but not with SR 49711, its low-affinity antipode. The potentiating effects of SR 48692 were positively related to the stimulation frequency (from 6 to 20 Hz) and to the dose of haloperidol (from 12.5 to 50 micrograms/kg) and were abolished after prior kainic acid lesion (1 microgram/1 microliter) of the nucleus accumbens. Thus, the effects of SR 48692 required the integrity of postsynaptic elements of the nucleus accumbens and occurred under the combination of two, at least partly, interdependent conditions: strong D2 autoreceptor blockade and high-intensity stimulation likely to release neurotensin. It is interesting that these potentiating effects of SR 48692 did not appear in the striatum. In conclusion, these findings suggest that endogenous neurotensin may attenuate the facilitation of D2 receptor blockade on mesolimbic but not nigrostriatal dopamine transmission.

Animals↗

PubMed1995

Pharmacological characterization of tachykinin receptors controlling acetylcholine release from rat striatum: an in vivo microdialysis study.

The regulation of striatal cholinergic function by tachykinins was examined in urethane-anesthetized rats by using microdialysis. Substance P (0.01-1 microM), [Sar9, Met (O2)11]substance P (1-10 microM), septide (0.1-3 microM), neurokinin (NK) A (0.1-10 microM), and senktide (0.1-10 microM) produced concentration-dependent increases in striatal acetylcholine (ACh) release. Septide was the most potent agonist for inducing release of ACh, whereas the stimulating effect of senktide was less pronounced and more progressive in onset. The response to septide was prevented by intraperitoneal administration of the nonpeptide NK1 antagonist SR 140333 (1-3 mg/kg) but not by the nonpeptide NK2 receptor antagonist SR 48968, indicating that the effect was mediated specifically by NK1 receptors. ACh release caused by NKA was reduced by SR 48968 (1-3 mg/kg) and slightly affected by SR 140333, indicating a principal role for NK2 receptors in the peptide response. The similar efficacy of SR 140333 and SR 48968 in blocking substance P-induced ACh release suggested that the effect of this peptide involves the stimulation of both NK1 and NK2 receptors. Finally, our results indicate that the increase in striatal ACh release induced by the D1 agonist (+)-SKF-38393 (3 microM) may be mediated indirectly through local release of NKA or substance P acting at NK2 receptors.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1995

Neuropharmacological profile of non-peptide neurotensin antagonists.

Neurotensin, an endogenous peptide widely distributed throughout the brain, fulfils neurotransmitter criteria. When administered centrally, neurotensin induces various effects and modulates the activity of the mesolimbic dopamine system. It antagonizes the behavioural action of dopamine in a manner similar, but not identical, to antipsychotic drugs. Neurotensin is even considered to be an endogenous neuroleptic. In fact, microinjection of neurotensin elicits different effects depending on both the dose and the cerebral structures into which the injection is made. Our work on the development of orally-active neurotensin antagonists has led to the identification of SR 48692, the first non-peptide antagonist of the neurotensin receptor, and some analogues. This small molecule reveals a surprising neuropharmacological profile. It antagonizes turning behaviour induced in mice and rats (after striatal or ventral tegmental area administration of neurotensin, respectively), hypolocomotion induced by intracerebroventricular injection of neurotensin in rats, and reverses the inhibitory effect of neurotensin (nucleus accumbens injection) on amphetamine-induced hyperlocomotion in rats. However, SR 48692 cannot reverse either dopamine release in the nucleus accumbens evoked by neurotensin injection in ventral tegmental area, or hypothermia and analgesia induced by intracerebroventricular injection of neurotensin. As direct and indirect dopamine agonists have been reported to promote neurotensin release in the cortex, behavioural studies were performed using injection of apomorphine. In these experiments, SR 48692 inhibited only turning and yawning. It did not antagonize other apomorphine-dependent effects such as climbing, hypothermia, hypo- or hyperlocomotion, penile erection and stereotypies. All together, these data raise the question of the existence of neurotensin receptor subtypes and confirm that the nature of neurotensin and dopamine interactions depends on the brain structures considered.

Animals↗

PubMed1995

[Recommendations for the diagnosis and therapy of insomnia. German Society of Sleep Research and Sleep Medicine DGSM].

There exist a variety of American and European recommendations regarding treatment with hypnotics, especially the duration of treatment. The German Sleep Society now publishes its own view to help physicians to cope with these different recommendations, some of which are contradictory. Therapy with hypnotics must include substantial information on the type of drug, dose, timing and duration as well as information about the possibility of interval treatment. Agonists at the benzodiazepine receptor, like the conventional benzodiazepines and zopiclone or zolpideme, are indicated in short-lasting adjustment insomnia as well as in long-lasting psychophysiological insomnia. Regarding the duration of prescription the German Sleep Society recommends a period of 14 days in de novo patients, which can be repeated once only. In persisting insomnias further approaches should disregard benzodiazepine receptor agonists, but rely on other classes of substances such as tricyclic antidepressants instead. If such approaches are ineffective, the intake of benzodiazepine receptor agonists may be extended to 6 months, when a sleep log and objective observations have documented a true sleep deficit, when daytime impairment arises, when daytime impairment arises, when rebound insomnia, organic or mental insomnias and dependencies have been excluded, and when the indication is monitored at 14-day intervals. If the insomnia persists, during and in spite of therapy a specialist in sleep medicine should be consulted. If therapy is still ineffective after 3 months of daily treatment, a sleep laboratory should be consulted.

Anti-Anxiety Agents↗

PubMed1995

[Subjective well-being in obstructive sleep apnea syndrome before and after nCPAP therapy].

18 obstructive sleep apnea patients (mean time of nCPAP-treatment: 412 nights) were asked about their subjective well-being before therapy and under treatment with nCPAP. Also their wifes were asked to give an outer appraisal. Both groups reported a clear reduction of general well-being before therapy and significant improvements in excessive daytime sleepiness, depression, physical and psychical complaints and the rate of patients accidents under nCPAP. In context with a good compliance of therapy these results indicate that the nCPAP-treatment was subjectively experienced as effective.

Adult↗

PubMed1994

Blockade of neurotensin receptors by the antagonist SR 48692 partially prevents retrograde axonal transport of neurotensin in rat nigrostriatal system.

The effect of SR 48692, a potent and selective non-peptide antagonist of the neurotensin receptor, was investigated on the retrograde axonal transport of neurotensin in the rat nigrostriatal dopamine pathway. When rats were injected in the striatum with (3-[125I]iodotyrosyl3)neurotensin, a substantial accumulation of radioactivity appeared in the ipsilateral substantia nigra 1.5 h after injection, and highest levels (336 +/- 23 dpm/mg of protein) were observed 2.5-3.5 h after the injection. The phenomenon required a pretreatment of the animals with thiorphan (30 micrograms) an inhibitor of endopeptidase. The amount of radioactivity accumulated (3.5 h) was found to be reduced (25%) by local (100 nM) or peripheral administration of SR 48692 (5, 10, 20 mg/kg, i.p.; 25%, 40%, 40%, respectively). Our results indicate that blockade of neurotensin receptors by a selective non-peptide receptor antagonist affects the retrograde axonal transport of the tridecapeptide, and further suggest the notion that this process involves neurotensin receptors.

Animals↗

PubMed1994

SR 48692, a non-peptide neurotensin receptor antagonist differentially affects neurotensin-induced behaviour and changes in dopaminergic transmission.

Unilateral microinjection of neurotensin in the ventral tegmental area of the rat (2.5 micrograms/0.5 microliter) produced behavioural excitation illustrated by contralateral circling. Given orally, SR 48692, a selective and potent non-peptide neurotensin receptor antagonist, significantly reduced these rotations with a triphasic dose-effect relationship. Inhibition occurred at 0.12 mg/kg; further increases in dose up to 2.5 mg/kg produced no significant antagonism, then at doses > or = 5 mg/kg, a second phase of antagonism was observed. Bilateral injection of neurotensin (0.5 microgram each side) into the nucleus accumbens antagonized the increase in locomotor activity following intraperitoneal injection of amphetamine. Given orally, SR 48692 reduced dose-dependently (0.1-1 mg/kg) these intra-accumbens neurotensin effects. Using high pressure liquid chromatography with electrochemical detection, we showed that microgram amounts of neurotensin injected into the ventral tegmental area increased dihydroxyphenylacetate/dopamine ratios in the nucleus accumbens. Using in vivo voltammetry techniques, we found that the injection of nanogram and picogram amounts of neurotensin in the ventral tegmental area stimulated dopamine efflux in the nucleus accumbens. None of these biochemical changes were affected by SR 48692 (0.1-10 mg/kg). These results indicate complex interactions between neurotensin and the mesolimbic dopamine system. More particularly, the differential ability of SR 48692 to affect neurotensin-evoked behavioural versus biochemical changes supports the concept of neurotensin receptor heterogeneity.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1994

Alfacalcidol (alpha D3) and calcium in osteoporosis.

In a prospective, randomized study, 66 osteoporotic postmenopausal women (mean age, 67 years) were scheduled to receive either alfacalcidol 0.25 microgram twice daily together with calcium 500 mg twice daily (treatment group, n = 24) or placebo twice daily with calcium 500 mg twice daily (control group, n = 42) for three years. In the treatment group, bone mineral content at the distal radius may have increased by 2% compared to a significant decrease of 7.8% in the control group. The difference between the two groups was also significant. Since the dose of alfacalcidol and calcium remained unadjusted, frequent hypercalciuria, as well as occasional mild, transient elevations of serum calcium, were observed in the treatment group. No changes in serum creatinine levels or creatinine clearance throughout the study were observed. The two groups did not differ with respect to the frequency of clinical side effects, which were mainly gastrointestinal and probably related to the calcium supplementation. Alfacalcidol and calcium may prevent further bone loss in women suffering from postmenopausal osteoporosis.

Absorptiometry, Photon↗

PubMed1993

In vitro and in vivo biological activities of SR140333, a novel potent non-peptide tachykinin NK1 receptor antagonist.

(S)1-(2-[3-(3,4-dichlorophenyl)-1-(3-isopropoxyphenylacetyl)pip eridin-3- yl]ethyl)-4-phenyl-1-azoniabicyclo[2.2.2]octane chloride (SR140333) is a new non-peptide antagonist of tachykinin NK1 receptors. SR140333 potently, selectively and competitively inhibited substance P binding to NK1 receptors from various animal species, including humans. In vitro, it was a potent antagonist in functional assays for NK1 receptors such as [Sar9,Met(O2)11]substance P-induced endothelium-dependent relaxation of rabbit pulmonary artery and contraction of guinea-pig ileum. Up to 1 microM, it had no effect in bioassays for NK2 ([beta Ala8]neurokinin A-induced contraction of endothelium-deprived rabbit pulmonary artery) and NK3 ([MePhe7]neurokinin B-induced contraction of rat portal vein) receptors. The antagonism exerted by SR140333 toward NK1 receptors was apparently non-competitive, with pD2' values (antagonism potency evaluated by the negative logarithm of the molar concentration of antagonist that produces a 50% reduction of the maximal response to the agonist) between 9.65 and 10.16 in the different assays. SR140333 also blocked in vitro [Sar9,Met(O2)11]substance P-induced release of acetylcholine from rat striatum. In vivo, SR140333 exerted highly potent antagonism toward [Sar9,Met(O2)11]substance P-induced hypotension in dogs (ED50 = 3 micrograms/kg i.v.), bronchoconstriction in guinea-pig (ED50 = 42 micrograms/kg i.v.) and plasma extravasation in rats (ED50 = 7 micrograms/kg i.v.). Finally, it also blocked the activation of rat thalamic neurons after nociceptive stimulation (ED50 = 0.2 micrograms/kg i.v.).

Animals↗

PubMed1993

SR 46559A: a novel and potent muscarinic compound with no cholinergic syndrome.

The cholinergic activities of SR 46559A, 3-[N-(2 diethyl-amino-2-methylpropyl)-6-phenyl-5-propyl] pyridazinamine sesquifumarate, have been investigated in vitro and in vivo, in rodents. Using rat brain cortical membranes, SR 46559A was a competitive ligand (Ki = 112 nM) at muscarinic M1 receptors, its affinity for muscarinic M2 (cardiac) and M3 (glandular) receptors being 6-7 times lower. SR 46559A did not interact with brain nicotinic receptors and high affinity choline uptake sites nor did it inhibit brain acetylcholinesterase activity. In contrast to reference muscarinic agonists, SR 46559A (1 mM) did not inhibit the forskolin-induced activation of cAMP synthesis nor did it stimulate phosphoinositides breakdown in various brain preparations. However, this compound enhanced (+67% at 1 mM) diacylglycerol formation in rat striatal miniprisms, an effect fully reversed by atropine. As shown with reference agonists, SR 46559A inhibited (IC50 = 10 microM) the K(+)-evoked release of [3H]GABA from rat striatal slices and reduced at 0.5 and 1 microM, the population spike amplitude of the CA1 pyramidal cells induced by stimulation of the Schaffer's collateral commissural pathway in rat hippocampal slices. In mice, SR 46559A at a near lethal dose (200 mg/kg PO) did not induce the typical cholinergic syndrome nor did it modify at 30 mg/kg PO the oxotremorine-induced hypothermia. Like muscarinic agonists, SR 46559A (1 mg/kg PO) potentiated haloperidol-induced catalepsy in rats and inhibited (ED50 = 0.12 mg/kg PO) rotations induced in mice by intrastriatal injection of pirenzepine.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholinesterase↗

PubMed1993

Disturbance of colour perception in Parkinson's disease.

A computer-aided method for the determination of colour fusion time (CFT) was developed. CFT indicates the acuity of the perception of monochromatic contours. CFT was determined in 36 patients with Parkinson's disease (PD) and compared with a group of 36 age- and sex-matched controls. Patients with PD generally had a shortened fusion time, especially for dark-green, light-blue and dark-red stimuli. The results give evidence to the hypothesis of a colour perception disorder in PD. The physiological and pathoanatomical basis of this phenomenon is unknown, but a functional deficit of cortical neurons may be a probable cause.

Adult↗

PubMed1993

Neuropharmacological profile of a novel and selective ligand of the sigma site: SR 31742A.

The biochemical, electrophysiological and behavioural effects of SR 31742A, a novel and selective ligand of sigma sites in brain, labelled with (+)-[3H]3PPP (Ki = 5.3 +/- 0.3 nM), were investigated in rodents and compared with those of DA antagonists having (haloperidol) or not (spiroperidol) a high affinity for sigma sites. Like haloperidol but unlike spiroperidol, SR 31742A, (ED50 = 0.065 mg/kg, i.p., and 0.21 mg/kg, p.o.) antagonized sigma-dependent turning behaviour in mice and inhibited (0.5 mg/kg, i.v.) the spontaneous firing of hippocampal (CA3) neurones in urethane-anaesthetized rats. In chloral hydrate-anaesthetized rats, like classical antipsychotic compounds, SR 31742A (0.625-5 mg/kg, i.p.) increased the number of spontaneously active A9 and A10 DA cells after single administration and produced an opposite effect after repeated injections. The drug SR 31742A reduced (2.5, 5, 10 mg/kg, i.p.) the hyperactivity elicited by various drugs including that produced by injection of (+)-amphetamine into the nucleus accumbens and impaired avoidance responses at doses (5, 10 mg/kg, i.p.), sparing escape behaviour. SR 31742A lacked affinity for DA receptors and neither did the compound induce catalepsy nor antagonize such effects elicited by apomorphine as climbing, hypothermia, stereotypy or the inhibition of firing of DA neurones. SR 31742A did not affect the basal metabolism of DA but at 10 mg/kg (i.p.) it significantly reduced the amphetamine-induced rise in levels of 3-MT in the striatum of mice. Together, these results indicate a modulatory role for sigma sites upon the activity of hippocampal and DA systems and that sigma ligands exert effects, which suggest antipsychotic potential.

Animals↗

PubMed1993

Protective effects of SR 57746A in central and peripheral models of neurodegenerative disorders in rodents and primates.

Compounds possessing neurotrophic properties may represent a possible treatment for neurodegenerative disorders such as Alzheimer's disease. SR 57746A, 1-[2-(naphth-2-yl)ethyl]-4-(3-trifluoromethylphenyl)-1,2,5,6- tetrahydropyridine hydrochloride, is a new compound with neurotrophic activity in a number of in vitro preparations. The neurotrophic effects of this compound have been evaluated in vivo using four distinct rat models of neurodegeneration: transient global ischaemia produced by a four-vessel occlusion; septohippocampal lesion produced by injection of vincristine sulphate into the medial septum; sciatic nerve crushing; and acrylamide-induced peripheral neuropathy. Rats were administered vehicle or 2.5-10 mg/kg p.o. SR 57746A, after initiation of the degenerative process, then once daily for 10 days in the first two models, 16 days in the third and 26 days in the fourth model. Median scores for ischaemia-induced neuronal damage were reduced by 30-40% by SR 57746A treatment in hippocampal CA1, CA2, and CA3 regions, and in the dorsal striatum. Twelve days after intraseptal vincristine administration, there was a marked loss of septohippocampal cholinergic neurons, as indicated by reduced choline acetyltransferase activity in both the septum and hippocampus. SR 57746A dose-dependently reversed this reduction in both areas. These results were confirmed by histoenzymological evaluation of hippocampal acetylcholinesterase content. SR 57746A also reversed the loss of hippocampal choline acetyltransferase induced by intraseptal vincristine in marmosets. Behavioral deficits in these models (exploratory behaviour in the former and short-term social memory in the latter) were also significantly reduced by SR 57746A treatment. In the sciatic crush model, sensorimotor function improved more rapidly in rats treated with 10 mg/kg SR 57746A. In this same model, SR 57746A (10 mg/kg/day) also significantly increased the length of regenerated nerve eight days after the crush, as measured using the pinch test. Finally, SR 57746A retarded the onset, reduced the amplitude and accelerated the recovery of acrylamide-induced peripheral neuropathy. Thus, SR 57746A possesses notable neurotrophic activity in a variety of neurodegenerative models in vivo, suggesting that the compound may possess therapeutic potential for the treatment of neurodegenerative diseases.

Acetylcholinesterase↗

PubMed1993

Findings of electroencephalographic brain mapping in mild to moderate dementia of the Alzheimer type during resting, motor, and music-perception conditions.

Sixteen-channel electroencephalographic (EEG) brain mapping studies were carried out under resting conditions in 41 patients with mild to moderate dementia of the Alzheimer type, diagnosed according to DSM-III-R criteria. The patients showed diffuse patterns of EEG slowing, as known from the literature. They showed increases of theta power in large bilateral brain areas and bitemporal increases of delta power as compared with both age-matched and younger control subjects. In addition, the patients had increased beta activity in comparison with the younger control group, but not with the age-matched control subjects. Functional brain mapping revealed decreases of EEG power during manual-motor and music-perception tasks in delta frequencies for patients, which was not seen in either of the two control groups. All frequency bands revealed major gender-related differences in EEG activity, which should receive more attention in future research.

Aged↗

PubMed1993

EEG mapping investigations of psychomotor and music perception brain dysfunction in untreated schizophrenic patients.

Twenty-six untreated schizophrenic inpatients and 34 control persons were investigated using 16-channel EEG mapping during resting, manumotor and music perception tasks. Power values of activation tasks were each referenced to a separate, immediately preceding resting condition, using conventional delta, theta, alpha and 2 beta frequency bands. Results in delta and alpha bands, which maximally separated the two groups, are reported only for space reasons. Results indicated a "nonreactivity" (in all frequency bands) on the two activation paradigms in schizophrenic patients as a group. Major gender effects were obtained in normal persons, but not signs of nonreactivity comparable to patients. Subdividing patients exclusively by means of their EEG changes on activation produced meaningful clinical subgroups of "positive/negative" schizophrenics. This latter finding could contribute towards clinical utility of EEG mapping in psychiatry.

Adult↗

PubMed1993

Biochemical and electrophysiological properties of SR 57746A, a new, potent 5-HT1A receptor agonist.

SR 57746A (1-[2-(naphth-2-yl) ethyl]-4-(3-trifluoromethylphenyl)-1, 2, 5, 6 tetra-hydropyridine hydrochloride) binds competitively, and with high affinity (Ki = 2.0 +/- 0.7 nM) to 5-HT1A receptors from rat hippocampus in vitro, but has much less affinity for other 5-HT receptor subtypes (IC50 > 650 nM). SR 57746A produces a concentration-dependent inhibition of forskolin-stimulated adenylate cyclase activity in rat hippocampal homogenates, with a maximal effect identical to that of 8-OH-DPAT, suggesting that SR 57746A behaves as a full agonist in this experimental model. SR 57746A potently displaces [3H]8-OH-DPAT binding to rat hippocampal membranes ex vivo, with an ID50 of 11.1 mg/kg po, 30 min after administration, and 2.8 mg/kg po, 2 h after administration. This effect of SR 57746A is long-lasting (at least 24 hours at 10 mg/kg po). SR 57746A does not modify the levels of 5-HT or DA in various brain areas, but decreases the concentrations of 5-HIAA, and increases those of DOPAC, HVA and 3-MT. Following i.v. administration, SR 57746A (0.095 to 0.25 mg/kg) inhibits the spontaneous firing of dorsal raphe neurones, but does not modify the activity of DA neurones in the substantia nigra or ventral tegmental area. Thus, SR 57746A is a potent, selective and full agonist at 5-HT1A receptors in vitro and vivo.

8-Hydroxy-2-(di-n-propylamino)tetralin↗