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S Arbilla

Publications and source records attributed to S Arbilla.

At least 37 records · Page 2Linked to original sources
PubMed1988

Limitations of the benzodiazepine receptor nomenclature: a proposal for a pharmacological classification as omega receptor subtypes.

At present, the nomenclature of benzodiazepine (BZ) receptors is based on historical association with the BZ structure. However, it is mainly through the new compounds chemically unrelated to BZ that the central and peripheral subtypes of BZ receptors have been characterized. We therefore propose the nomenclature of a Greek letter omega, as omega 1, omega 2, and omega 3 to designate the central BZ1, BZ2, and peripheral BZ receptors, respectively. Among the several classes of non-BZD drugs with affinity for different receptors, the imidazopyridines provide a valuable tool for the characterization of omega receptor subtypes. Most BZ are nonselective ligands for the central omega 1 and omega 2 receptors, while selectivity for omega 1 receptor subtypes is present in several non BZ chemical series: imidazopyridines (zolpidem), triazolopyridazines (CL 218872), betacarbolines (beta-CCE), and pyrazoloquinolines (CGS 8216). Selective ligands for the omega 2 subtype are not available so far. The so-called peripheral BZ receptor is also present in the central nervous system; therefore, the proposed nomenclature of omega 3 receptors resolves this paradox because it does not designate location and is defined in terms of pharmacological specificity. Selective ligands for omega 3 receptors include the BZ Ro 5-4864, and the isoquinolinecarboxamide PK 11195, while the imidazopyridine alpidem is the ligand with the highest affinity for this receptor subtype.

Animals↗
PubMed1988

Ifenprodil and SL 82.0715 as cerebral anti-ischemic agents. II. Evidence for N-methyl-D-aspartate receptor antagonist properties.

The effects of the anti-ischemic agents ifenprodil and its derivative SL 82.0715 ((+/-)-alpha-(4-chlorophenyl)-4-[(4-fluorophenyl) methyl]-1-piperidineethanol] have been analyzed in a number of models indicative of N-methyl-D-aspartate (NMDA) antagonistic potential in vitro and in vivo. Ifenprodil and SL 82.0715 potently and noncompetitively antagonize the stimulatory effects of NMDA on cyclic GMP production in immature rat cerebellar slices (IC50 values, 0.4 and 10 microM, respectively), as well as the NMDA-evoked [3H]acetylcholine release in adult rat striatal slices (IC50 values, 1.6 and 6.6 microM, respectively). Ifenprodil is 10 times more potent than (+/-)3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) but less active than the reference noncompetitive NMDA channel blockers [MK 801, ((+)-5-methyl-10,11-dihydro-5H-dibenzo-[a,d]cyclohepten-5,10-imine ], phencyclidine and 1-[1-(2-thienyl)cyclohexyl]piperidine (TCP)] in these models. Ifenprodil and SL 82.0715 partially displace (maximal displacement 40-50% at 10 microM) the NMDA receptor ligand [3H]CPP from its binding site to rat brain membranes (IC50 values, 0.1 and 0.3 microM, respectively) in a noncompetitive manner; in the micromolar range the two agents also partially displace the NMDA channel ligand [3H]TCP from its binding site to rat brain membranes, and noncompetitively antagonize the L-glutamate-induced increase in [3H]TCP binding. Ifenprodil (0.01-1 microM) partially antagonizes the depolarizing effects of NMDA on the immature rat hemisected spinal cord in vitro. In mouse cultured spinal cord neurons, ifenprodil dose-dependently antagonizes the depolarizing effects of micropressure applied NMDA. Inhibition of the effects of NMDA in this model by ifenprodil and SL 82.0715 is noncompetitive. In vivo and after systemic i.p. administration, ifenprodil and SL 82.0715 antagonize the stimulatory effects of intrastriatally dialyzed NMDA on striatal dopamine release in rats (ID50 values, 0.9 and 0.3 mg/kg, respectively), and block the harmaline-evoked increase in cerebellar cyclic GMP production in mice (ID50 values, 3 and 4 mg/kg, respectively). These results indicate that ifenprodil is a noncompetitive NMDA antagonist which has a mechanism of action distinct from either the reference competitive NMDA receptor antagonists (CPP and 2-amino-5-phosphonovalerate) or the noncompetitive NMDA channel blockers (phencyclidine, TCP and MK 801). The potent NMDA antagonistic effects of the ifenprodil class of compounds are likely to be related to the demonstrated anti-ischemic potential of these compounds.

Animals↗
PubMed1987

A functional response to D1 dopamine receptor stimulation in the central nervous system: inhibition of the release of [3H]-serotonin from the rat substantia nigra.

The influence of dopamine receptor agonists on the calcium dependent electrically-evoked release of [3H]-serotonin was studied in the superfused rat substantia nigra. The electrically-evoked overflow of [3H]-serotonin was significantly inhibited by micromolar concentrations of exogenous dopamine and of the D1-selective dopamine receptor agonists, fenoldopam and SKF 38393. The inhibitory effects of dopamine and fenoldopam on [3H]-serotonin release were antagonized by the D1-selective dopamine receptor antagonist SCH 23390. S-sulpiride, an antagonist of D2 receptors failed to antagonize the inhibitory effects of dopamine on [3H]-serotonin release. Moreover, quinperol, the selective D2 receptor agonist did not modify the electrically evoked release of [3H]-serotonin. In the presence of nomifensine, SCH 23390 but not S-sulpiride enhanced in a concentration dependent manner the electrically-evoked release of [3H]-serotonin. Under similar experimental conditions, exposure to fenoldopam did not inhibit the electrically-evoked release of [3H]-serotonin from rat hippocampal or hypothalamic slices. These results indicate that, in rat substantia nigra, exogenous as well as endogenous dopamine causes inhibition of serotonin release by activation of dopamine receptors of the D1-subtype.

Animals↗
PubMed1987

Autoradiographic localization of [3H]zolpidem binding sites in the rat CNS: comparison with the distribution of [3H]flunitrazepam binding sites.

The regional distribution of [3H]zolpidem, a novel imidazopyridine hypnotic possessing preferential affinity for the BZD1 (benzodiazepine subtype 1) receptor, has been studied autoradiographically in the rat CNS and compared with that of [3H]flunitrazepam. The binding of [3H]zolpidem to rat brain sections was saturable, specific, reversible, and of high affinity (KD = 6.4 nM). It occurred at a single population of sites whose pharmacological characteristics were similar to those of the benzodiazepine receptors labeled with [3H]flunitrazepam. However, ethyl-beta-carboline-3-carboxylate and CL 218,872 were more potent displacers of [3H]zolpidem than of [3H]flunitrazepam. The autoradiographic brain distribution of [3H]zolpidem binding sites was qualitatively similar to that previously reported for benzodiazepine receptors. The highest levels of [3H]-zolpidem binding sites occurred in the olfactory bulb (glomerular layer), inferior colliculus, ventral pallidum, nucleus of the diagonal band of Broca, cerebral cortex (layer IV), medial septum, islands of Calleja, subthalamic nucleus, and substantia nigra pars reticulata, whereas the lowest densities were found in parts of the thalamus, pons, and medulla. Comparative quantitative autoradiographic analysis of the binding of [3H]zolpidem and [3H]flunitrazepam [a mixed BZD1/BZD2 (benzodiazepine subtype 2) receptor agonist] in the CNS revealed that the relative density of both 3H-labeled ligands differed in several brain areas. Similar levels of binding for both ligands were found in brain regions enriched in BZD1 receptors, e.g., substantia nigra pars reticulata, inferior colliculus, cerebellum, and cerebral cortex lamina IV. The levels of [3H]zolpidem binding were five times lower than those of [3H]flunitrazepam binding in those brain regions enriched in BZD2 receptors, e.g., nucleus accumbens, dentate gyrus, and striatum. Moreover, [3H]zolpidem binding was undetectable in the spinal cord (which contains predominantly BZD2 receptors). Finally, like CL 218,872 and ethyl-beta-carboline-3-carboxylate, zolpidem was a more potent displacer of [3H]flunitrazepam binding in brain regions enriched in BZD1 receptors than in brain areas enriched in BZD2 receptors. The present data add further support to the view that zolpidem, although structurally unrelated to the benzodiazepines, binds to the benzodiazepine receptor and possesses selectivity for the BZD1 receptor subtype.

Animals↗
PubMed1987

Fengabine, a novel antidepressant GABAergic agent. II. Effect on cerebral noradrenergic, serotonergic and GABAergic transmission in the rat.

The effects of fengabine (a novel benzylidene derivative possessing clinically demonstrated antidepressant action) on neurochemical parameters related to norepinephrine, serotonin and gamma-aminobutyric acid (GABA) neurons have been investigated in the rat and mouse brain. When given acutely, fengabine (50-1000 mg/kg i.p.) does not alter norepinephrine uptake but accelerates the turnover rate of norepinephrine in the rat brain as demonstrated by the enhancement of: the alpha-methyl-p-tyrosine-induced disappearance of norepinephrine in the hypothalamus; 3,4-dihydroxyphenylacetic acid levels in noradrenergic cell body areas; the pargyline-induced accumulation of normetanephrine in the hypothalamus; and 3,4-dihydroxyphenylethyleneglycol levels in the hypothalamus, septum and spinal cord. No tolerance to the effect of fengabine on the latter biochemical parameter was observed after repeated treatment for 2 weeks at doses of 100 or 200 mg/kg i.p., b.i.d. Fengabine (100 or 200 mg/kg i.p., b.i.d.), given for 14 days, causes a desensitization of isoprenaline-stimulated adenylate cyclase in septal and cortical slices of the rat but fails to modify cortical beta, alpha-1 or alpha-2 adrenoceptor binding sites. Fengabine (up to 400 mg/kg i.p.) has no effect on rat cerebral serotonin uptake, synthesis or metabolism. Moreover, when given subacutely (100 or 200 mg/kg i.p., b.i.d. for 2 weeks), it fails to alter rat cortical serotonine receptors or [3H]imipramine binding sites. Fengabine (up to 50-100 microM) is also inactive in vitro on [3H] GABA binding to GABAA or GABAB receptors in the rat brain or on GABA transaminase activity in the mouse brain.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Newly synthesized noradrenaline mediates the alpha 2-adrenoceptor inhibition of [3H]5-hydroxytryptamine release induced by beta-phenylethylamine in rat hippocampal slices.

In slices of the rat hippocampus, alpha 2-adrenoceptors located presynaptically on serotonergic nerve terminals modulate the electrically evoked calcium-dependent release of [3H]serotonin [( 3H]5HT). We have investigated the effects of a naturally occurring trace amine, beta-phenylethylamine (beta-PEA), on noradrenergic transmission in the rat hippocampus. Under experimental conditions in which MAO of type B is inhibited by deprenyl-exposure to beta-PEA (0.1-10 microM) facilitates the spontaneous outflow of [3H]noradrenaline and inhibits the electrically evoked release of [3H]5HT. The inhibitory effect of beta-PEA (3 microM) on the evoked release of [3H]5HT was antagonized by the alpha 2-adrenoceptor antagonist idazoxan at 1 microM, and by pretreatment with alpha-methyl-p-tyrosine (alpha-MpT, 300 mg/kg i.p., 2 h). The inhibition of tyrosine hydroxylase activity by alpha-MpT does not modify the inhibition of the evoked release of [3H]5HT by the alpha 2-adrenoceptor agonist, 6-fluoronoradrenaline, or the serotonin receptor agonist, 5-methoxytryptamine. Pretreatment with the neurotoxin DSP4 (50 mg/kg i.p., 10 days) markedly antagonized the inhibitory action of beta-PEA on [3H]5HT release. These results indicate that the noradrenaline-releasing action of beta-PEA inhibits the electrically evoked release of [3H]5HT through the activation of alpha 2-adrenoceptors. This inhibitory effect appears to be mediated exclusively through the release of newly synthesized noradrenaline, and does not involve the direct activation by beta-PEA of the inhibitory 5HT autoreceptors which modulate [3H]5HT release in the rat hippocampus.

Animals↗
PubMed1986

High affinity [3H]zolpidem binding in the rat brain: an imidazopyridine with agonist properties at central benzodiazepine receptors.

[3H]Zolpidem, a novel hypnotic drug possessing a chemical structure unrelated to that of benzodiazepine (BZD) was employed as a new ligand to determine its binding characteristics to membrane preparations of rat cerebral cortex and cerebellum. In both structures, the imidazopyridine [3H]zolpidem bound with high affinity to a single population of recognition sites. The cerebellum possessed a similar number of [3H]zolpidem and [3H]diazepam binding sites, while the cerebral cortex possessed a lower density of [3H]zolpidem than [3H]diazepam binding sites. In contrast to [3H]diazepam binding, [3H]zolpidem binding was not detectable in the spinal cord. In the cortex, BZDs had a similar potency to displace [3H]zolpidem and [3H]diazepam binding while non-BZDs were more potent to inhibit [3H] zolpidem binding than [3H]diazepam binding. The binding of [3H]zolpidem was enhanced by GABA to the same extent as [3H]diazepam binding. The increase in [3H] zolpidem binding caused by chloride ions was less pronounced than that in [3H]diazepam binding. It is concluded that [3H]zolpidem possesses selectivity for BZD receptors with the pharmacological characteristics and regional distribution of the BZD1 receptor subtype. [3H]Zolpidem as a radioligand offers a useful additional tool to study the mechanism of action of hypnotics acting through BZD receptor subtypes.

Animals↗
PubMed1986

Electrical stimulation releases 3H-betaxolol from rat atrial slices: possible role of noradrenergic nerves.

Under in vitro conditions, 3H-betaxolol was accumulated in rat atrial slices, reaching a tissue-medium ratio of 12.3 +/- 1.8 ml/g. This process was temperature-dependent, but ouabain-resistant. 3H-Betaxolol accumulated in atrial slices was subsequently released by electrical stimulation. The electrically-evoked release of 3H-betaxolol was abolished in the absence of calcium, and reduced in the presence of bretylium 10 microM. After surgical sympathetic denervation by stellate ganglionectomy there was a marked reduction in the endogenous content of noradrenaline and in the retention of 3H-noradrenaline in atrial slices. The concomitant decrease in the amount of 3H-noradrenaline released by electrical stimulation following denervation was modest, although statistically significant. Following sympathetic denervation, the tissue retention of 3H-betaxolol was not significantly affected, but the release of 3H-betaxolol by electrical stimulation was considerably reduced. After pretreatment with reserpine the amount of radioactivity released by electrical stimulation from slices labelled with 3H-betaxolol or 3H-noradrenaline was markedly reduced. The tissue retention of 3H-noradrenaline was reduced to a larger extent than that of 3H-betaxolol following the administration of reserpine. The simultaneous release of noradrenaline and betaxolol by nerve stimulation observed under our experimental conditions may represent a mechanism through which betaxolol can reach selectively the postsynaptic beta 1-adrenoceptors and reinforce beta-adrenoceptor blockade in the heart.

Adrenergic beta-Antagonists↗
PubMed1986

Phenylethylamine-induced release of noradrenaline fails to stimulate alpha 1-adrenoceptors modulating [3H]-acetylcholine release in rat atria, but activates alpha 2-adrenoceptors modulating [3H]-serotonin release in the hippocampus.

The modulation of the depolarization induced release of [3H]-acetylcholine by agonists acting on alpha-adrenoceptors was studied in superfused rat atrial slices. In this model, noradrenaline and methoxamine, but not UK 14304 reduced the potassium evoked release of [3H]-acetylcholine. The inhibitory action of these drugs was antagonized by the alpha 1 selective adrenoceptor antagonist prazosin. Propranolol, idazoxan and sulpiride did not antagonize the inhibition by noradrenaline of the potassium-evoked release of [3H]-acetylcholine. Exposure to amphetamine, beta-phenylethylamine, m- or p-tyramine, increased in a concentration-dependent manner the spontaneous outflow of [3H]-noradrenaline from atrial slices. Yet, these concentrations of the indirectly acting sympathomimetic amines, tested in the presence of an inhibitor of monoamine oxidase (MAO), failed to modify the potassium evoked release of [3H]-acetylcholine. Desipramine 3 mumol/l or cocaine 10 mumol/l did not affect the release of [3H]-acetylcholine evoked by potassium stimulation. Under similar experimental conditions, beta-phenylethylamine facilitated the spontaneous outflow of [3H]-noradrenaline, and inhibited the electrically-evoked release of [3H]-serotonin from the hippocampus by activation of alpha 2-adrenoceptors. It is concluded that the release of acetylcholine from atrial cholinergic neurons can be modulated through inhibitory alpha 1-adrenoceptors, which are not activated when the release of noradrenaline is induced by indirectly acting sympathomimetic amines. In addition, amphetamine or structurally related amines do not activate directly recognition sites in the cholinergic postganglionic parasympathetic neuron to modify the release of [3H]-acetylcholine.

Acetylcholine↗
PubMed1985

Rapid desensitization of presynaptic dopamine autoreceptors during exposure to exogenous dopamine.

When nomifensine is employed to inhibit neuronal uptake, exposure to dopamine (DA) (0.1-0.3 microM) or apomorphine (0.01-0.1 microM) inhibited, in a concentration-dependent manner, the electrically evoked release of [3H]dopamine from slices of the rabbit caudate nucleus. Apomorphine inhibited transmitter release independently of the time of exposure to the drug (6-32 min). On the other hand, the inhibitory effect of exogenous dopamine occurred only if a short period (4-12 min) of exposure was employed. In studies on the electrically evoked release of [3H]acetylcholine in slices of the rabbit caudate nucleus there was no evidence for desensitization to apomorphine or exogenous dopamine at the level of the dopamine receptors that inhibit [3H]acetylcholine release. These results indicate that the dopamine autoreceptors modulating [3H]dopamine release in the caudate nucleus become subsensitive after a few minutes of exposure to exogenous dopamine. This effect does not occur at the level of the dopamine receptors which inhibit the release of [3H]acetylcholine.

Acetylcholine↗
PubMed1985

Inhibition by yohimbine of the calcium-dependent evoked release of [3H]GABA in rat and mouse brain slices in vitro.

Calcium-dependent release of [3H]GABA was elicited by electrical stimulation in slices of rat and mouse cerebral cortex or by potassium stimulation in the mouse brain-stem. The stimulation-evoked release of [3H]GABA was inhibited by yohimbine in a concentration-dependent manner. High concentrations of other alpha-adrenoceptor antagonists such as phentolamine, RS 21361, idazoxan, rauwolscine and corynanthine also inhibited [3H]GABA release. This effect was not observed with pseudoyohimbine or prazosin. [3H]GABA release was not affected by exposure to the alpha-adrenoceptor agonists clonidine, M7, noradrenaline or methoxamine. In addition, clonidine did not antagonize the yohimbine-induced inhibition of [3H]GABA release. The inhibitory effect of yohimbine did not result from an interaction with endogenously released noradrenaline since the inhibition was still observed in reserpine-pretreated animals. It is concluded that yohimbine and other alpha 2-adrenoceptor antagonists inhibit the stimulation-evoked release of [3H]GABA through a mechanism which appears to be independent of the blockade of alpha 2-adrenoceptors and which does not involve an interaction with endogenous noradrenaline. The present results indicate that yohimbine exerts non-specific actions on the release of [3H]GABA and that similar effects can be observed with other alpha-adrenoceptor blocking agents in high concentrations. Consequently, when studying the effects of yohimbine and other alpha 2-adrenoceptor antagonists on noradrenergic neurotransmission, the possibility of non-specific effects should be taken into consideration, particularly in the high concentrations range.

Animals↗
PubMed1985

[3H] beta-phenylethylamine but not [3H](+)-amphetamine is released by electrical stimulation from perfused rat striatal slices.

Perfused rat striatal slices were prelabelled with either [3H](+)-amphetamine or [3H] beta-phenylethylamine. Electrical stimulation released a significant amount of radioactivity only from the slices prelabelled with [3H] beta-phenylethylamine. The electrically evoked release of radioactivity from slices labelled with [3H] beta-phenylethylamine was entirely calcium-dependent and was abolished after pretreatment with reserpine (5 mg/kg s.c., 24 h). In addition, S-sulpiride (1 microM), which facilitates the electrically evoked release of radioactivity from slices labelled with [3H]DA by blocking dopamine autoreceptors, also induced an increase of the radioactivity released by electrical stimulation from slices labelled with [3H] beta-phenylethylamine. Our results indicate that, in spite of the structural similarities between AMPH and PEA, only the latter which is the naturally occurring analog of AMPH can be released by electrical stimulation in a calcium-dependent manner.

Amphetamine↗
PubMed1985

Influence of GABA mimetics and lithium on biochemical manifestations of striatal dopamine target cell hypersensitivity.

The potential mechanisms whereby GABA mimetics and the antimanic agent lithium stabilize dopaminergic transmission are discussed. Evidence is presented that GABA mimetics, and in particular progabide, affect dopamine-mediated events in the basal ganglia on at least three levels. First, they reduce dopamine neuron activity in both the basal and the activated states. Secondly, on a long-term basis, they antagonize the proliferation of striatal dopamine receptors subsequent to chronic neuroleptic treatment. Thirdly, they modulate the expression of dopamine receptor activation by acting distally to the dopaminergic synapse. Lithium and GABA mimetics have the last two properties in common. These effects may represent the biochemical basis for the therapeutic action of GABA mimetics in iatrogenic dyskinesias. Moreover, the similarity between the biochemical effects of GABA mimetics and lithium suggest that the former drugs may have a therapeutic potential in mania.

Animals↗
PubMed1985

Amphetamine induced release of endogenous dopamine in vitro is not reduced following pretreatment with reserpine.

The release of endogenous dopamine evoked by electrical stimulation or by exposure to (+)-amphetamine (10 microM) was determined in superfused striatal slices of the rat. The spontaneous and the electrically-evoked release of dopamine were significantly increased in the presence of nomifensine (10 microM). After reserpine pretreatment (5 mg/kg, s.c., 24 h), the striatal dopamine content was reduced by about 90%. Exposure to 10 microM (+)-amphetamine during 2 min released similar amounts of dopamine from striatal slices of untreated or reserpine pretreated rats. Similar results were obtained when monoamine oxidase activity was inhibited in vivo with pargyline. Pretreatment with reserpine does not modify the (+)-amphetamine-induced release of dopamine, in spite of the marked reduction of the striatal dopamine content. These results provide direct evidence for the view that (+)-amphetamine releases dopamine from a special, reserpine-resistant pool of newly synthetized transmitter.

Animals↗
PubMed1985

Sodium dependent [3H]cocaine binding associated with dopamine uptake sites in the rat striatum and human putamen decrease after dopaminergic denervation and in Parkinsons disease.

The binding of radiolabelled cocaine, an inhibitor of dopamine uptake, to the post-mortem human putamen was studied and compared to that in the rat striatum. Saturation analysis of [3H]cocaine binding to the human putamen revealed the presence of a high affinity component of binding with a Kd of 0.21 mumol/l and a Bmax of 1.47 pmol/mg protein. In addition a low affinity component (Kd = 26.4 mumol/l) was demonstrated, having a Bmax of 42.2 pmol/mg protein. Also in the rat striatum [3H]cocaine binding was both of high affinity (Kd = 0.36 mumol/l, Bmax = 5.56 pmol/mg protein) and low affinity (Kd = 25.9 mumol/l, Bmax = 35.6 pmol/mg protein). A pharmacological characterisation of high affinity [3H]cocaine binding to rat striatal membranes clearly indicates an association with the neuronal dopamine transporter. The IC50 values of 8 selected drugs for inhibition of [3H]cocaine binding in the rat striatum were highly significantly correlated with their potency to inhibit [3H]dopamine uptake into slices of the rat striatum. [3H]Cocaine binding was stereospecifically inhibited by (+)nomifensine and (+)diclofensine which were 50-80-fold more active than their respective (-)isomers. Drugs with dopamine releasing activity were more potent at inhibiting [3H]dopamine uptake than at competing for the high affinity site of [3H]cocaine binding. A highly significant correlation was found between IC50 values for [3H]cocaine binding in the rat striatum and the human putamen. Further evidence in support of an association of [3H]cocaine binding in the rat striatum with the dopamine transporter was obtained from lesion studies. Thus, intranigral 6-hydroxydopamine administration produced a marked (67%) decrease in striatal [3H]cocaine binding.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Pharmacological profile of the imidazopyridine zolpidem at benzodiazepine receptors and electrocorticogram in rats.

Zolpidem is a novel non-benzodiazepine related hypnotic, which possesses an imidazopyridine structure. This drug has preferential affinity for the 3H-diazepam binding site in the rat cerebellum, while it is only weakly active at inhibiting 3H-Ro 5-4864 binding to the rat kidney. The potency of zolpidem at displacing 3H-Ro 15-1788 binding to rat cerebral cortex membranes is enhanced in the presence of GABA. On the sleep pattern of the electrocorticogram in the curarised rat, zolpidem induces a physiological type of slow wave sleep with rapid onset of action. Zolpidem differs from classical benzodiazepine drugs, in possessing an atypical binding profile to 3H-benzodiazepine receptors, and because it does not affect the sleep patterns.

Animals↗
PubMed1985

Inhibition of the electrically evoked release of [3H]acetylcholine in rat striatal slices: an experimental model for drugs that enhance dopaminergic neurotransmission.

The activation by endogenous dopamine of the inhibitory 3,4-dihydroxyphenylethylamine (dopamine) receptors modulating the electrically evoked release of [3H]acetylcholine [( 3H]ACh) and [3H]dopamine in rat striatal slices is a function of the concentration of dopamine accumulated in the synaptic cleft during electrical stimulation. When the release of 3H-neurotransmitters was elicited with a 2-min period of stimulation at a frequency of 1 Hz, neither dopamine autoreceptors nor dopamine receptors modulating [3H]ACh were activated by endogenously released dopamine. On the other hand, exposure to (S)-sulpiride facilitated the release of [3H]dopamine and [3H]ACh elicited when the 2-min stimulation was carried out at a frequency of 3 Hz but this effect was not observed at a lower frequency of stimulation (1 Hz). In the presence of amphetamine the dopamine receptors modulating the electrically evoked release of [3H]ACh can be activated by endogenous dopamine even at the lower frequency of stimulation (1 Hz). Similar effects can be obtained if the neuronal uptake of dopamine is inhibited by cocaine or nomifensine. The inhibition by amphetamine of the release of [3H]ACh elicited by electrical stimulation at 1 Hz involves dopamine receptors and can be fully antagonized by clozapine, haloperidol, chlorpromazine, or pimozide. The stereoselectivity of this antagonism can be demonstrated with the optical enantiomers of sulpiride and butaclamol. This inhibitory effect of amphetamine on cholinergic neurotransmission appears to be the result of the stimulation of dopamine receptors of the D2 subtype, as they were resistant to blockade by the preferential D1 receptor antagonist SCH 23390.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗