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PubMed2004

Production of 5alpha-reduced neurosteroids is developmentally regulated and shapes GABA(A) miniature IPSCs in lamina II of the spinal cord.

In lamina II of the spinal dorsal horn, synaptic inhibition mediated by ionotropic GABA(A) and glycine receptors contributes to the integration of peripheral nociceptive messages. Whole-cell patch-clamp recordings were performed from lamina II neurons in spinal cord slices to study the properties of miniature IPSCs (mIPSCs) mediated by activation of GABA(A) and glycine receptors in immature (<30 d) and adult rats. Blockade of neurosteroidogenesis by 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinoline carboxamide (PK11195), an inhibitor of the peripheral benzodiazepine receptor (PBR), or finasteride, which blocks 5alpha-reductase, accelerated the decay kinetics of GABA(A) receptor-mediated mIPSCs in immature, but not in adult animals. Glycine receptor-mediated mIPSCs remained unaffected under these conditions. These results suggest the presence of a tonic production of 5alpha-reduced neurosteroids in young rats that confers slow decay kinetics to GABA(A) mIPSCs. At all of the ages, selective stimulation of PBR by diazepam in the presence of flumazenil prolonged GABA(A) mIPSCs in a PK11195- and finasteride-sensitive manner. This condition also increased the proportion of mixed GABA(A)/glycine mIPSCs in the immature animals and led to the reappearance of mixed GABA(A)/glycine mIPSCs in the adult. Our results might point to an original mechanism by which the strength of synaptic inhibition can be adjusted locally in the CNS during development and under physiological and/or pathological conditions by controlling the synthesis of endogenous 5alpha-reduced neurosteroids.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed2002

3beta -hydroxypregnane steroids are pregnenolone sulfate-like GABA(A) receptor antagonists.

Endogenous neurosteroids have rapid actions on ion channels, particularly GABA(A) receptors, which are potentiated by nanomolar concentrations of 3alpha-hydroxypregnane neurosteroids. Previous evidence suggests that 3beta-hydroxypregnane steroids may competitively antagonize potentiation induced by their 3alpha diastereomers. Because of the potential importance of antagonists as experimental and clinical tools, we characterized the functional effect of 3beta-hydroxysteroids. Although 3beta-hydroxysteroids reduced the potentiation induced by 3alpha-hydroxysteroids, 3beta-hydroxysteroids acted noncompetitively with respect to potentiating steroids and inhibited the largest degrees of potentiation most effectively. Potentiation by high concentrations of barbiturates was also reduced by 3beta-hydroxysteroids. 3beta-Hydroxysteroids are also direct, noncompetitive GABA(A) receptor antagonists. 3beta-Hydroxysteroids coapplied with GABA significantly inhibited responses to > or =15 microm GABA. The profile of block was similar to that exhibited by sulfated steroids, known blockers of GABA(A) receptors. This direct, noncompetitive effect of 3beta-hydroxysteroids was sufficient to account for the apparent antagonism of potentiating steroids. Mutated receptors exhibiting decreased sensitivity to sulfated steroid block were insensitive to both the direct effects of 3beta-hydroxysteroids on GABA(A) responses and the reduction of potentiating steroid effects. At concentrations that had little effect on GABAergic synaptic currents, 3beta-hydroxysteroids and low concentrations of sulfated steroids significantly reversed the potentiation of synaptic currents induced by 3alpha-hydroxysteroids. We conclude that 3beta-hydroxypregnane steroids are not direct antagonists of potentiating steroids but rather are noncompetitive, likely state-dependent, blockers of GABA(A) receptors. Nevertheless, these steroids may be useful functional blockers of potentiating steroids when used at concentrations that do not affect baseline neurotransmission.

Amino Acid Substitution↗
PubMed1999

Antagonist-induced reversal of functional and structural measures of hippocampal benzodiazepine tolerance.

One week oral flurazepam (FZP) administration in rats results in anticonvulsant tolerance in vivo, tolerance measured in vitro in hippocampal CA1 pyramidal cells, and regulation of hippocampal gamma-aminobutyric acid(A)-receptor subunit protein expression. A single injection (4 or 20 mg/kg i.p) of the benzodiazepine antagonist flumazenil (FLM) was given 1 day after FZP treatment, and tolerance and subunit protein expression were evaluated 1 day later. In vivo tolerance was measured by a reduced ability of the alpha(1)-subunit-selective agonist zolpidem to suppress pentylenetetrazole-induced seizures. This tolerance was reversed by 20 but not 4 mg/kg FLM. In in vitro hippocampal slices, there was tolerance to the effect of zolpidem to prolong the decay of pyramidal cell miniature inhibitory postsynaptic currents, which was reversed by FLM (4 mg/kg) pretreatment. A reduction in miniature inhibitory postsynaptic current amplitude ( approximately 50%) was also restored by FLM injection. [(3)H]Zolpidem binding measured 0, 2, and 7 days after FZP treatment was significantly decreased in the hippocampus and cortex at 0 days but not thereafter. Changes in alpha(1)- and beta(3)-subunit protein expression were examined via quantitative immunohistochemical techniques. alpha(1)-Subunit protein levels were down-regulated in the CA1 stratum oriens and beta subunit levels were up-regulated in the stratum oriens and stratum radiatum of the CA3 region. Chronic FZP effects on alpha(1)- and beta(3)-subunit protein levels were also reversed by prior FLM injection. FLM's effect on both functional and structural correlates of benzodiazepine tolerance suggests that each of these measures plays an interdependent role in mediating benzodiazepine tolerance.

Animals↗
PubMed1999

Discriminative stimulus effects of zolpidem in squirrel monkeys: comparison with conventional benzodiazepines and sedative-hypnotics.

The present study examined whether zolpidem, an imidazopyridine with selectivity for benzodiazepine (BZ)/gamma-aminobutyric acid(A) receptors containing the alpha1-subunit, had discriminative stimulus effects similar to typical BZs and other sedative/hypnotic drugs in primates. Squirrel monkeys (Saimiri sciureus) were trained to discriminate zolpidem (1.0 mg/kg i.v.) from vehicle under a 10-response fixed-ratio schedule of food delivery. Under test conditions, zolpidem (0.1-3.0 mg/kg) increased responding on the drug lever to an average maximum of 90% of total responding. When pretreatment times were varied from 5 to 50 min, the discriminative stimulus effects of zolpidem were maximal at 5 min and near control levels 35 min after administration. Flumazenil antagonized both the discriminative stimulus and rate-decreasing effects of zolpidem in a dose-dependent and surmountable fashion (in vivo apparent pA(2) values of 7.3 and 6.6 for the discriminative stimulus and rate-suppressing effects, respectively). The BZs triazolam, midazolam, diazepam, and N-desmethyldiazepam engendered dose-related increases in drug-lever responding that reached zolpidem-like levels (90%) in the majority of monkeys tested. In contrast, lorazepam, chlordiazepoxide, and oxazepam engendered average maximums of 70% or less and substituted fully for zolpidem in one or two monkeys only. Representative barbiturates as well as drugs that bind to non-BZ sites (muscimol, baclofen, buspirone, cyproheptadine, diphenhydramine) engendered 0 to 45% of responses on the drug lever up to doses that markedly reduced response rate. These results support the view that zolpidem's selectivity for the alpha1-subunit of the BZ/gamma-aminobutyric acid(A) receptor complex confers a distinctive profile of interoceptive effects that overlaps partially with those of typical BZs but not with those of barbiturates.

Animals↗
PubMed1999

Central benzodiazepine involvement in clonidine cardiovascular actions.

It is well known that the GABAergic and noradrenergic systems play an important role in blood pressure and heart rate regulation. Benzodiazepines and beta-carbolines, respectively, increase or decrease the probability of chloride-channel opening induced by GABA. The aim of this study was to determine, in conscious rats, the interaction existing between the central alpha2-adrenoceptor stimulation induced by clonidine and the facilitation or impairment of benzodiazepine receptor activity through the administration of either diazepam, a benzodiazepine receptor agonist, or methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM), an inverse benzodiazepine agonist. Clonidine (5-10 microg, intracerebroventricularly) reduced heart rate and increased mean blood pressure by activation of central alpha2-adrenoceptors. Diazepam (2 mg/kg, intravenously (i.v.)) induced an increase in heart rate, while DMCM (0.3 mg/kg, i.v.) elicited a bradycardic effect. The bradycardic effects induced by both clonidine and DMCM were antagonized by the prior administration of methylatropine (1.5 mg/kg, i.v.). DMCM (0.3 mg/kg, i.v.) prevented the clonidine effects on heart rate and mean blood pressure, while diazepam (2 mg/kg, i.v.) failed to modify these effects. Our results suggest that the bradycardic effects of clonidine are mediated by a vagal stimulation and are related to the activation of a GABAergic pathway.

Adrenergic alpha-2 Receptor Agonists↗
PubMed2000

Comparative kinetics and response to the benzodiazepine agonists triazolam and zolpidem: evaluation of sex-dependent differences.

Eighteen healthy volunteers (10 men and 8 women) participated in a single-dose, double-blind, three-way crossover pharmacokinetic and pharmacodynamic study. Treatment conditions were 0.25 mg of triazolam, a full-agonist benzodiazepine ligand; 10 mg of zolpidem, an imidazopyridine having relative selectivity for the type 1 benzodiazepine receptor subtype; and placebo. Weight-normalized clearance of triazolam was higher in women than in men (8.7 versus 5. 5 ml/min/kg), but the difference was not significant. In contrast, zolpidem clearance was lower in women than in men (3.5 versus 6.7 ml/min/kg, P <.06). Compared to placebo, both active medications produced significant benzodiazepine agonist-like pharmacodynamic effects: sedation, impaired psychomotor performance, impaired information recall, and increased electroencephalographic beta-amplitude. Effects of triazolam and zolpidem in general were comparable and less than 8 h in duration. There was no evidence of a substantial or consistent sex difference in pharmacodynamic effects or in the kinetic-dynamic relationship, although subtle differences could not be ruled out due to low statistical power. The complete dependence of triazolam clearance on CYP3A activity, as opposed to the mixed CYP participation in zolpidem clearance, may explain the differing sex effects on clearance of the two compounds.

Adult↗
PubMed2000

GABAC receptors are localized with microtubule-associated protein 1B in mammalian cone photoreceptors.

Protein MAP1B was recently reported to link GABA(C) receptors to the cytoskeleton at neuronal synapses. This interaction was demonstrated in the mammalian retina, where GABA(C) receptors were thought to be exclusively expressed in bipolar cells. Our previous studies on cultured photoreceptors suggested however the presence of GABA(C) receptors in cones. To further investigate GABA(C) receptor expression in cones, we measured GABA responses in mammalian photoreceptors in situ, and we examined the distribution of the receptor and that of protein MAP1B in the mammalian outer retina. Photoreceptors were recorded from flat-mounted retinas of retinal degeneration mice at an age when the retina becomes cone-dominated after rod cell death. GABA(A) and GABA(C)-gated currents were produced only in cones but not rods. Recording freshly dissociated retinal cells from wild-type C57 mice confirmed the presence of GABA(A) and GABA(C) receptors in cones. Immunohistochemical labeling of mouse and rat retinal sections localized GABA(C) receptors to cone terminals that were identified by peanut agglutinin lectin staining. As expected from previous studies on bipolar cells, the punctate immunostaining was not restricted to cone terminals in the outer plexiform layer. MAP1B immunolabeling was obtained in rat and pig retinas and was similarly found in cone terminals identified by the peanut agglutinin lectin staining. These results provide physiological and histological evidence that cones receive a GABA feedback in the mammalian retina and are consistent with the notion that protein MAP1B links GABA(C) receptors to the cytoskeleton at postsynaptic sites.

Animals↗
PubMed2001

[Benzodiazepines and benzodiazepine receptor agonists in the treatment of sleep disorders--importance and dangers. Evaluation from the clinical medical view].

After first giving an overview about the epidemiological situation, the indications and contraindications of benzodiazepines as well as those of the newer short-time hypnotics zolpidem and zopiclone are reviewed. Premises for their use and alternatives to their application are discussed and the different substances are discussed for their clinical use. Problems of drug abuse and addiction are accounted in detail for these effective and little toxic agents. Finally recommendations for treatment are given to contribute to a more critical and scientific way of prescribing these valuable, though problematic, drugs.

Anti-Anxiety Agents↗
PubMed2003

Concerted GABAergic actions of Aplysia feeding interneurons in motor program specification.

GABAergic inhibitory interneurons regulate the activity of diverse types of neural networks, but the specific roles of these interneurons in motor control are poorly understood. In the Aplysia feeding motor network, three interneurons, cerebral-buccal interneuron-3 (CBI-3) and buccal interneurons B40 and B34, are GABA-immunoreactive and evoke fast IPSPs in their postsynaptic followers. Using a combination of pharmacological experiments with GABA antagonists, agonists, and uptake inhibitors, we found that these fast IPSPs are likely mediated by GABA. Functionally, these fast IPSPs specify two parameters for ingestive motor programs elicited by the command-like interneuron CBI-2: (1) the appropriate phasing of activity of the radula closer motor neuron B8 relative to protraction-retraction, and (2) protraction duration. First, in ingestive programs, B8 activity is phased such that it fires minimally during protraction. CBI-3 and B40 exert fast inhibition to minimize B8 activity during protraction, by either acting directly on B8 (B40) or indirectly on B8 (CBI-3). Second, these ingestive programs are characterized by long protraction duration, which is promoted by B40 and B34 because hyperpolarization of either cell shortens protraction. Such effects of B40 and B34 are attributable, at least partly, to their inhibitory effects on the retraction-phase interneuron B64 whose activation terminates protraction. Consistent with a GABAergic contribution to both B8 phasing and protraction duration, blockade of GABAergic inhibition by picrotoxin increases B8 activity during protraction and shortens protraction, without disrupting the integrity of motor programs. Thus, the concerted actions of GABAergic inhibition from three Aplysia feeding interneurons contribute to the specification of multiple features that define the motor program as an ingestive one.

Animals↗
PubMed2003

Synchronization of kainate-induced epileptic activity via GABAergic inhibition in the superfused rat hippocampus in vivo.

We studied cellular mechanisms of synchronization of epileptiform activity induced by kainic acid in a novel preparation of superfused rat hippocampus in vivo. Under urethane anesthesia, kainate induced epileptic population spikes occurring at 30-40 Hz. Pyramidal cells fired exclusively during population spikes with an average probability of 0.34 on rebound of rhythmic GABA(A)-mediated inhibitory postsynaptic events. Excitatory synaptic events contributed little to seizure activity. Rhythmic epileptiform activity was suppressed by blocking GABA(A) receptors and was slowed by barbiturates. Thus, GABAergic inhibition is instrumental in synchronizing kainate-induced epileptiform rhythmic activity in the gamma frequency band in the intact hippocampus in vivo.

Action Potentials↗
PubMed2003

Sildenafil improves acquisition and retention of memory in mice.

Sildenafil (Viagra) has been introduced recently in market to correct male impotency and has gained immense popularity for its dramatic effects all over the world. The present study was designed to investigate the effect of sildenafil on learning and memory in mice using elevated plus maze. A total of XV groups of animals were employed in the present study. Central cholinergic pathways play a crucial role in learning and memory processes. Physostigmine, an anticholinesterase agent (0.5 mg, 1.0 mg kg(-1), i.p) was employed for its memory enhancing property and alprazolam a benzodiazepine receptor agonist served as a memory-impairing agent. In the present study, alprazolam produced anterograde amnesia (at 0.5 mg kg(-1), i.p) and retrograde amnesia (at 0.25 mg, 0.5 mg, 0.75 mg kg(-1), i.p.) in separate groups of animals. Caffeine at 5 mg, 10 mg and 20 mg kg(-1), i.p. (an established psychostimulant) did not show any significant change in learning and memory of mice. Sildenafil (at 8 mg kg(-1), i.p.) administered 30 minutes prior to training on first day produced a marginal decrease in transfer latency time on first day; whereas, sildenafil (at 2 mg, 4 mg, 8 mg kg(-1), i.p.) administered immediately after training on first day produced a dose-dependent improvement of memory in mice. However, further studies need to be carried out to elucidate the underlying mechanism of sildenafil as a memory enhancer.

Alprazolam↗
PubMedDate not supplied

[Participation of GABA--benzodiazepine receptor complex in the anxiolytic effect of piracetam].

It is established that bicuculline, picrotoxin, and flumazenil (agents blocking different sites of GABA receptor) decrease the anxiolytic effect of piracetam as manifested in the conflict situation test. The most pronounced interaction was observed between piracetam and flumazenyl. On the background of antagonist action, piracetam inhibited the effects of flumazenil (but not those of bicuculline and picrotoxin). Based on these data, it is assumed that the anxiolytic effect of piracetam is mediated to some extent by benzodiazepine site of the GABA-benzodiazepine receptor complex.

Animals↗
PubMed1995

Regulation of allosteric coupling and function of stably expressed gamma-aminobutyric acid (GABA)A receptors by chronic treatment with GABAA and benzodiazepine agonists.

Chronic treatments with drugs that stimulate or potentiate gamma-aminobutyric acid (GABA)A receptor function cause uncoupling of allosteric sites and downregulation of the GABAA receptors expressed in neurons. To study these effects on receptors having a defined subunit composition, we treated stably transfected mouse Ltk- cells (PA3 cells) with drugs known to uncouple GABAA receptors. Because dexamethasone controls the expression of bovine alpha-1, beta-1 and gamma 2L GABAA receptor subunit genes in PA3 cells, this expression system provides a way to study receptors in the absence of neuronal subunit gene promoters. We assayed binding of [3H]flunitrazepam to measure allosteric coupling and uptake of 36Cl- to measure GABAA receptor function. Chronic (4 day) treatment of PA3 cells with muscimol, GABA or flunitrazepam reduced the GABA enhancement of binding of [3H]flunitrazepam to PA3 cells. Chronic flurazepam or muscimol treatments also caused downregulation of benzodiazepine potentiation of muscimol-stimulated 36Cl- uptake. Chronic treatment with muscimol did not affect levels of subunit mRNAS and alpha 1- or beta 1-subunit protein of GABAA receptors and chronic flunitrazepam did not affect subunit mRNAs or alpha 1 protein. We conclude that chronic drug treatments regulate allosteric coupling and function of GABAA receptors in stably transfected cells and this regulation cannot be attributed to decreases in the expression of receptor subunits or to expression of subunits other than alpha 1 beta 1 or gamma 2L.

Allosteric Regulation↗
PubMed1995

Drug discrimination analysis of midazolam under a three-lever procedure. II: Differential effects of benzodiazepine receptor agonists.

Twelve rats were trained to discriminate 0.32 and 3.2 mg/kg s.c. midazolam from no drug under a three-lever, multiple trials drug discrimination procedure. In cumulative dose-response tests, midazolam s.c. (0.032-10 mg/kg) and i.p. (0.1-10 mg/kg) occasioned dose-dependent increases first in 0.32 mg/kg (low-dose) lever responding and then in 3.2 mg/kg (high-dose) lever responding. The benzodiazepines diazepam (0.032-18 mg/kg) and triazolam (0.0032-3.2 mg/kg) produced patterns of generalization similar to that of midazolam; however, chlordiazepoxide (0.1-32 mg/kg), lorazepam (0.032-10 mg/kg), flurazepam (0.01-10 mg/kg), bretazenil (0.01-32 mg/kg) and the imidazopyridazine zolpidem (0.032-3.2 mg/kg) dose-dependently occasioned > 80% responding on the low- but not the high-dose midazolam lever. Clonazepam (0.1-10 mg/kg) occasioned 0% responding on the high-dose lever, but also failed to occasion full generalization to the low-dose midazolam lever in 40% of the rats. Bretazenil has been well-characterized as a partial benzodiazepine agonist and zolpidem as benzodiazepine-receptor-subtype selective; the present results are consistent with their partial or selective agonist effects in those other paradigms. The differential effects of the classic 1,4 benzodiazepine agonists tested suggest that the discriminative stimulus effects of these other compounds may be more differentiable than previous drug discrimination studies have suggested. This three-choice drug discrimination procedure appears to be a useful model for studying relative intrinsic efficacies of this class of compounds.

Animals↗
PubMed1995

Comparison of benzodiazepine receptor ligands with partial agonistic, antagonistic or partial inverse agonistic properties in precipitating withdrawal in squirrel monkeys.

Benzodiazepine receptor (BZR) ligands previously characterized as differing in intrinsic efficacy were evaluated first for potency in antagonizing flunitrazepam-induced sleep in monkeys. Data from these experiments were used to define approximately equieffective doses for subsequent use in precipitating withdrawal in diazepam-treated monkeys. It was shown that partial agonists with intermediate intrinsic efficacy (bretazenil, Ro 41-7812) were relatively ineffective in precipitating withdrawal reactions in diazepam-treated squirrel monkeys. The potent and specific BZR antagonist flumazenil, which possesses weak intrinsic efficacy, was more effective in precipitating a withdrawal reaction in diazepam-treated monkeys. In contrast, the highest dose of the BZR antagonist ZK 93426 that could be administered failed to precipitate withdrawal under the same experimental conditions. Finally, the BZR partial inverse agonist sarmazenil was the most effective of these BZR ligands in eliciting a precipitated withdrawal reaction. Thus, the results of the present investigation strongly suggest that BZR ligands differing in intrinsic efficacy differentially precipitate withdrawal in squirrel monkeys treated chronically with diazepam.

Animals↗
PubMed1997

Barbiturate-like actions of the propanediol dicarbamates felbamate and meprobamate.

Felbamate and meprobamate are structurally related propanediol dicarbamates that possess distinct pharmacological profiles. Felbamate is a minimally sedative, broad-spectrum anticonvulsant, whereas meprobamate is a strong sedative-anxiolytic agent. Previously, we reported that felbamate potentiates gamma-aminobutyric acid(A) (GABA(A)) receptor Cl- currents and inhibits N-methyl-D-aspartate (NMDA) receptor currents. Here we further characterized the interaction of the two dicarbamates with GABA(A) receptors to determine the basis for their pharmacological differences. In whole-cell voltage-clamp recordings from cultured rat hippocampal neurons, meprobamate enhanced GABA-evoked responses in a concentration-dependent manner and, at high concentrations (>1 mM), exhibited a separate channel-blocking effect that limited the magnitude of GABA(A) receptor potentiation. At equivalent concentrations, meprobamate produced substantially greater potentiation than did felbamate. Furthermore, meprobamate (but not felbamate), in the absence of GABA, directly activated Cl- currents that could be attenuated by the GABA(A) receptor antagonists bicuculline and picrotoxin. The mean deactivation time constant of whole-cell currents evoked by 10 mM meprobamate (110 ms) or 1 and 3 microM GABA (180 ms) were faster than the deactivation time constant of 10 mM meprobamate (490 ms) or 3 mM felbamate (470 ms) in the presence of GABA. Meprobamate and felbamate prolonged the mean burst duration of GABA-activated unitary currents in excised outside-out membrane patches. In addition, at high (supratherapeutic) concentrations, meprobamate blocked NMDA-activated currents. We conclude that felbamate and meprobamate have barbiturate-like modulatory actions on GABA(A) receptors, but meprobamate has greater activity and, unlike felbamate, is able to directly activate the receptor.

Animals↗
PubMed1997

Stimulatory effect of diazepam on gastric acid secretion in the continuously perfused stomach in rats under urethane anesthesia.

The effects of diazepam, a typical benzodiazepine receptor agonist, on gastric acid secretion were studied in both conscious pylorus-ligated rats and the perfused stomach of rats under urethane anesthesia. Diazepam did not affect acid secretion in conscious pylorus-ligated rats. Under urethane anesthesia, diazepam showed a definite stimulation on gastric acid secretion. However this stimulatory action was caused neither by 4'-chlordiazepam, which is a peripheral benzodiazepine receptor agonist, nor beta-carbline-3-carboxylic acid methyl ester, which is an inverse benzodiazepine receptor agonist. Pretreatment with atropine, hexamethonium or bilateral truncal vagotomy inhibited the diazepam-induced acid secretion. Pretreatment with flumazenil, which is a benzodiazepine receptor antagonist, reduced the acid secretion induced by diazepam, but pretreatment with 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxam ide, which is a peripheral benzodiazepine receptor antagonist, did not reduce the acid secretion induced by diazepam. 3-Mercaptopropionic acid, which is an inhibitor of GABA biosynthesis, picrotoxin and pentylenetetrazol inhibited diazepam-stimulated acid secretion. Gastric acid secretion stimulated by baclofen was not affected by flumazenil, 3-mercaptopropionic acid or picrotoxin. These results suggest that acid secretion is centrally stimulated by diazepam in rats under anesthesia, and the stimulatory action is closely associated with benzodiazepine-GABA complex receptors.

3-Mercaptopropionic Acid↗