SEARCH · PubMed Health

Results for “Pyrazines”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 703 records · Page 39Linked to original sources

PubMed1993

Effects of d-fenfluramine, MK-212, and ondansetron on saline drinking in two-choice tests in the rehydrating rat.

The aim of the present studies was to investigate the effects of serotonergic compounds on preference for isotonic saline and aversion to hypertonic saline, respectively. Twenty-two-hour water-deprived rats were divided into two groups: The first was given a choice between 0.9% saline and water in a 30-min test; the second was given a choice between 1.8% saline and water. Animals were tested following administration of d-fenfluramine, the 5-HT1C receptor agonist 6-chloro-2-(1-piperazinyl)pyrazine (MK-212), and the 5-HT3 receptor antagonist ondansetron. d-Fenfluramine (0.3-3.0 mg/kg) did not reduce 0.9% saline preference; instead, at 0.3 mg/kg there was a significant increase in saline drinking. In contrast, MK-212 (0.3-3.0 mg/kg) abolished the preference for isotonic saline whereas ondansetron (10-100 micrograms/kg) had no effect. d-Fenfluramine and MK-212 reduced hypertonic saline drinking, although at the highest dose for each drug water drinking was also reduced. These data add further to the evidence for an important serotonergic involvement in the control of saline drinking and preference in the rat.

Animals↗

PubMed1992

Rates of interactions of superoxide with vitamin E, vitamin C and related compounds as measured by chemiluminescence.

The rate constants for the interactions of superoxide with vitamin E (alpha-tocopherol), vitamin C (ascorbic acid) and their related compounds have been measured by a chemiluminescence method. A strong chemiluminescence of a constant intensity was observed when xanthine oxidase was added to an aqueous solution of hypoxanthine and a Cypridina luciferin analog, 2-methyl-6-phenyl-3-7-dihydroimidazo[1,2-a]pyrazin-3-one (CLA). Vitamin E, vitamin C and their related compounds competed with CLA to react with superoxide and reduced the chemiluminescence intensity. From a kinetic analysis of the effect of addition of these compounds on the chemiluminescence intensity, the rate constants for their interactions with superoxide were measured at 25 degrees C and pH 7.8. The rate constants were obtained as 3.3 x 10(5) and 1.7 x 10(4) M-1 s-1 for ascorbate and 2-carboxy-2,5,7,8-tetramethyl-6-chromanol, respectively, and also as 4.9 x 10(3) and 4.5 x 10(3) M-1 s-1 for alpha-tocopherol incorporated into soybean and dimyristoyl phosphatidylcholine liposomal membranes, respectively. It has been shown that this method is a sensitive and a quick method which can be applied for measurement of the reactivities of various natural and synthetic compounds toward superoxide. In addition it has been shown that this method can also be applied to the heterogeneous system as well as homogeneous solution, which makes it more versatile and useful for the study in biochemistry.

Ascorbic Acid↗

PubMed1994

Blunted oral body temperature response to MK-212 in cocaine addicts.

Previous studies have suggested that chronic cocaine administration may affect serotonergic function and that serotonin (5-HT) may be of importance in cocaine craving. Ten male cocaine addicts and 28 male normal controls were challenged with MK-212 (6-chlor-2-[1-piperazinyl]-pyrazine) (20 mg), a direct acting 5-HT receptor agonist which has affinity for a variety of 5-HT receptor subtypes, and placebo, on separate days. The plasma cortisol and prolactin (PRL) concentrations and oral body temperature responses to MK-212 and placebo were compared between groups. The temperature response to MK-212 was significantly blunted in cocaine addicts compared to normal controls. However, the plasma cortisol and PRL responses to MK-212 did not differ between the two groups. These results suggest selective alteration of presynaptic 5-HT1A or postsynaptic 5-HT2A/2C function in cocaine addicts.

Adult↗

PubMed1991

Simple and accurate determination of methylpyrazines in biofluids using high-performance liquid chromatography.

The determination of six methylpyrazines was performed using high-performance liquid chromatography (HPLC). Methylpyrazines were simultaneously extracted and injected onto a silica gel column with a syringe-type minicolumn packed with diatomaceous earth granules. The extraction-injection solvent used was dichloromethane and the mobile phase solvent for HPLC was dichloromethane containing 0.08% of 1.65 M ammonia solution and 0.5% of methanol. Methylpyrazines were detected using an ultraviolet detector set at 275 nm. Linear relationships between the amount of sample and peak height were confirmed from 50 ng/ml to 10 micrograms/ml of the biofluids. When an aliquot of 10 microliters of biofluid was introduced to the minicolumn, the detection limit of methylpyrazines was as low as 30 ng/ml with each pyrazine derivative. The method is simple and accurate and is thus applicable to pharmacokinetic studies which are performed on animals. The results showed that the possible pharmacological effects of methylpyrazines might be evaluated pharmacokinetically using this newly developed technique.

Animals↗

PubMed2005

Supraphysiological concentrations of 5-aminolevulinic acid dimerize in solution to produce superoxide radical anions via a protonated dihydropyrazine intermediate.

5-aminolevulinic acid (ALA) is the committed biological precursor to porphyrins. At supraphysiological concentrations ALA can dimerize to form 3,6-dihydropyrazine-2,5-dipropanoic acid (DHPY), which transfers electrons to XTT in a reaction that does not require metal ions and is specifically inhibited by superoxide dismutase. The formation of DHPY from ALA follows dimerization kinetics with a pK of 7.8+/-0.1. At pH 11.2, DHPY is relatively stable, but when the pH is dropped to 6.0 rapid conversion to 2,5-(beta-carboxyethyl)pyrazine occurs via an intermediate with an absorption maximum of 370 nm. Formation of this intermediate is pH-dependent with a pK of 6.0+/-0.1. These data indicate that ALA dimerizes to produce superoxide from a protonated form of DHPY. The significance of these results with respect to the concentrations of ALA used in photodynamic therapy, and the increased incidence of liver cancer in acute intermittent porphyria, is discussed.

Aminolevulinic Acid↗

PubMed2006

Determination of H2O2-dependent generation of singlet oxygen from human saliva with a novel chemiluminescence probe.

Singlet oxygen (1O2) has been shown to play an important role in salivary defense system, but its generation process and level from human saliva remain uncertain due to the lack of a reliable detection method. We have previously reported 4,4'(5')-bis[2-(9-anthryloxy)ethylthio]tetrathiafulvalene (BAET) as a novel chemiluminescence probe for 1O2. In this work, the probe is successfully used to characterize H2O2-dependent generation of 1O2 from saliva in real time. However, the yield of 1O2 is found to be very low, for example, being about 0.13 nmol from 200 microL saliva in the presence of 1 mM of hydrogen peroxide over a 5-s reaction period. The result is also compared with that obtained with another 1O2 probe 2-methyl-6-phenyl-3,7-dihydroimidazo[1,2-a]pyrazin-3-one (CLA), demonstrating that, besides 1O2, the other reactive oxygen species such as hydroxyl radical may also be involved in the reaction of saliva with H2O2. Furthermore, the present study shows that the selectivity of BAET for 1O2 is much higher than that of CLA and thus BAET is highly suited for the detection of 1O2 in the presence of other reactive oxygen species in biological systems.

Anthracenes↗

PubMed2004

Nitroreductase catalyzed biotransformation of CL-20.

Previously, we reported that a salicylate 1-monooxygenase from Pseudomonas sp. ATCC 29352 biotransformed CL-20 (2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaaza-isowurtzitane) (C(6)H(6)N(12)O(12)) and produced a key metabolite with mol. wt. 346 Da corresponding to an empirical formula of C(6)H(6)N(10)O(8) which spontaneously decomposed in aqueous medium to produce N(2)O, NH(4)(+), and HCOOH [Appl. Environ. Microbiol. (2004)]. In the present study, we found that nitroreductase from Escherichia coli catalyzed a one-electron transfer to CL-20 to form a radical anion (CL-20(-)) which upon initial N-denitration also produced metabolite C(6)H(6)N(10)O(8). The latter was tentatively identified as 1,4,5,8-tetranitro-1,3a,4,4a,5,7a,8,8a-octahydro-diimidazo[4,5-b:4',5'-e]pyrazine [IUPAC] which decomposed spontaneously in water to produce glyoxal (OHCCHO) and formic acid (HCOOH). The rates of CL-20 biotransformation under anaerobic and aerobic conditions were 3.4+/-0.2 and 0.25+/-0.01 nmol min(-1)mg of protein(-1), respectively. The product stoichiometry showed that each reacted CL-20 molecule produced about 1.8 nitrite ions, 3.3 molecules of nitrous oxide, 1.6 molecules of formic acid, 1.0 molecule of glyoxal, and 1.3 ammonium ions. Carbon and nitrogen products gave mass-balances of 60% and 81%, respectively. A comparative study between native-, deflavo-, and reconstituted-nitroreductase showed that FMN-site was possibly involved in the biotransformation of CL-20.

Aza Compounds↗

PubMed2005

Stereospecific recognition of a spirosuccinimide type aldose reductase inhibitor (AS-3201) by plasma proteins: a significant role of specific binding by serum albumin in the improved potency and stability.

AS-3201 [(3R)-2'-(4-bromo-2-fluorobenzyl)spiro[pyrrolidine-3,4'(1'H)-pyrrolo[1,2-a]pyrazine]-1',2,3',5(2'H)-tetrone] is a structurally novel and stereospecifically potent aldose reductase (AKR1B; EC 1.1.1.21) inhibitor, which contains a succinimide ring that undergoes ring-opening at physiological pH levels. To delineate intermolecular interactions governing its favorable pharmacokinetic profile, the interaction of AS-3201 (R-isomer) with plasma proteins, especially human serum albumin (HSA), was examined in comparison with that of the optical antipode (S-isomer). Fluorescence, kinetic, and high-performance frontal analyses showed that the R-isomer is more strongly bound than the S-isomer to sites I and II on HSA, and the R-isomer is particularly protected from hydrolysis, suggesting that the stable HSA-R-isomer complex contributes to its prolonged activity. The thermodynamic parameters for the specific binding indicated that in addition to hydrophobic interactions, hydrogen bonds contribute significantly to the R-isomer complex formation. (13)C NMR observations of the succinimide ring (5-(13)C enriched), which are sensitive to its ionization state, suggested the presence of a hydrogen bond between the R-isomer and HSA, and (19)F NMR of the pendent benzyl ring (2-(19)F) evaluated the equilibrium exchange dynamics between the specific sites. Furthermore, fatty acid binding or glycation (both are site II-oriented perturbations) inhibited the binding to one of the specific sites and reduced the stereospecificity of HSA toward the isomers, although the clinical influence of these perturbations on the R-isomer binding ratio seemed to be minor. Thus, the difference in the interaction mode at site II might be a major cause of the stereospecificity; this is discussed on the basis of putative binding modes. The present results, together with preliminary absorption and distribution profiles, provide valuable information on the stereospecific pharmacokinetic and pharmacodynamic properties of the R-isomer relevant for the therapeutic treatment of diabetic complications.

Aldehyde Reductase↗

PubMed2006

Design of molecular wires based on supramolecular structures for application in glucose biosensors.

In the present work, the synthesis and the spectroelectrochemical characterization of a novel iron compound derived of tetra-2-pyridyl-1,4-pyrazine (TPPZ) with hexacyanoferrate species forming a very stable supramolecular complex in the presence of polypyrrole (PPY) matrix, is described. The hybrid material has shown excellent catalytic activity towards H(2)O(2) detection that makes it suitable for being used as redox mediator in a glucose biosensor. The hybrid FeTPPZFeCN/PPY film presents satisfactory detection limits and high sensitivity for H(2)O(2) in the presence of K(+) or Na(+) ions. For the glucose biosensor, a linear range up to 1.1 mmoll(-1) of glucose was observed with no interferences. In this case, the sensitivities obtained were 7.88 and 5.90 microAmmol(-1)lcm(-2) in phosphate buffer or NaCl solutions, respectively. The good sensitivity is related to the presence of a high-dimensional structure based on polypyridine type ligands providing an "electron antennae effect" facilitating electron tunneling between the protein and the electrode.

Biosensing Techniques↗

PubMed2004

Synthesis and biological evaluation of 2,3-diarylpyrazines and quinoxalines as selective COX-2 inhibitors.

Several 2,3-diaryl pyrazines and quinoxalines with 4-sulfamoyl (SO(2)NH(2))/methylsulfonyl (SO(2)Me)-phenyl pharmacophores have been synthesized and evaluated for the cyclooxygenase (COX-1/COX-2) inhibitory activity. Smaller groups such as methoxy, methyl and fluoro when substituted at/around position-4 of the adjacent phenyl ring, have great impact on the selective COX-2 inhibitory activity of the series. Many potential compounds were obtained from a brief structure-activity relationship (SAR) study. Two of these, compounds 11 and 25 exhibited excellent in vivo activity in the established animal model of inflammation. Since compound 25 possessed an amenable sulfonamide group, two of its prodrugs 48 and 49 were also synthesized. Both of them have excellent in vivo potential, and represent a new class of COX-2 inhibitor.

Animals↗

PubMed2005

Synthesis of alkyne derivatives of a novel triazolopyrazine as A(2A) adenosine receptor antagonists.

A novel [1,2,4]triazolo[1,5-a]pyrazine core was synthesized and coupled with terminal acetylenes. The structure-activity relationship of the alkynes from this novel template was studied for their in vitro and in vivo adenosine A(2A) receptor antagonism. Selected compounds from this series were shown to have potent in vitro and in vivo activities against adenosine A(2A) receptor. Compound 12, in particular, was found to be orally active at 3mg/kg in both a mouse catalepsy model and a 6-hydroxydopamine-lesioned rat model.

Adenosine A2 Receptor Antagonists↗

PubMed2005

Pyrazoloheteroaryls: novel p38alpha MAP kinase inhibiting scaffolds with oral activity.

A test library with three novel p38alpha inhibitory scaffolds and a narrow set of substituents was prepared. Appropriate combination of substituent and scaffold generated potent p38alpha inhibitors, for example, pyrazolo[3,4-b]pyridine 9, pyrazolo[3,4-d]pyrimidine 18a and pyrazolo[3,4-b]pyrazine 23b with potent in vivo activity upon oral administration in animal models of rheumatoid arthritis.

Administration, Oral↗

PubMed2005

Pharmacokinetics and pharmacodynamics of sitagliptin, an inhibitor of dipeptidyl peptidase IV, in healthy subjects: results from two randomized, double-blind, placebo-controlled studies with single oral doses.

BACKGROUND: Sitagliptin (MK-0431 [(2R)-4-oxo-4-(3-[trifluoromethyl]-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7[8H]-yl)-1-(2,4,5-trifluorophenyl)butan-2-amine]) is an orally active, potent, and selective inhibitor of dipeptidyl peptidase IV (DPP-IV) currently in phase III development for the treatment of type 2 diabetes. METHODS: Two double-blind, randomized, placebo-controlled, alternating-panel studies evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of single oral doses of sitagliptin (1.5-600 mg) in healthy male volunteers. RESULTS: Sitagliptin was well absorbed (approximately 80% excreted unchanged in the urine) with an apparent terminal half-life ranging from 8 to 14 hours. Renal clearance of sitagliptin averaged 388 mL/min and was largely uninfluenced by the dose administered. The area under the plasma concentration-time curve for sitagliptin increased in an approximately dose-dependent manner and was not meaningfully influenced by food. Single doses of sitagliptin markedly and dose-dependently inhibited plasma DPP-IV activity, with approximately 80% or greater inhibition of DPP-IV activity occurring at 50 mg or greater over a 12-hour period and at 100 mg or greater over a 24-hour period. Compared with placebo, sitagliptin produced an approximately 2-fold increase in postmeal active glucagon-like peptide 1 levels. Sitagliptin was well tolerated and was not associated with hypoglycemia. CONCLUSIONS: This study provides proof of pharmacologic characteristics for sitagliptin in humans. By inhibiting plasma DPP-IV activity, sitagliptin increases the postprandial rise in active glucagon-like peptide 1 concentrations without causing hypoglycemia in normoglycemic healthy male volunteers. Sitagliptin possesses pharmacokinetic and pharmacodynamic characteristics that support a once-daily dosing regimen.

Administration, Oral↗

PubMed2005

Synthesis of 2,6-diphenylpyrazine derivatives and their DNA binding and cytotoxic properties.

A series of 2,6-diphenylpyrazine derivatives was synthesized from 2,6-dichloropyrazine and 4-methoxyphenylboronic acid using palladium(0) as catalyst in a Suzuki methodology. After deprotection of the hydroxyl, alkylation reactions with different halides afforded compounds 5-8 bearing hydrophilic chains. DNA binding and cytotoxic properties were investigated. Compound 11 bearing imidazoline terminal groups was found to be a potent AT-specific DNA minor groove binder but there was no relationship between DNA interaction and cytotoxicity. However, in all cases the incorporation of the pyrazine ring was found to promote the cytotoxicity of the molecules compared to the corresponding pyridine analogues, previously synthesized.

Animals↗

PubMed2005

Anxiolytic-like effect of a serotonergic ligand with high affinity for 5-HT1A, 5-HT2A and 5-HT3 receptors.

S-(-)-2-[[4-(napht-1-yl)piperazin-1-yl]methyl]-1,4-dioxoperhydropyrrolo[1,2-alpha]-pyrazine (CSP-2503) is a serotonin (5-HT) receptor ligand with selectivity and high affinity for 5-HT1A, 5-HT2A and 5-HT3 receptors. CSP-2503 reduced rectal temperature and 5-HT neuronal hypothalamic activity in mice, decreased electrical activity of raphe nuclei cells in rats and blocked the enhancement of adenylate cyclase activity induced by forskolin in HeLa cells transfected with the human 5-HT1A receptor. This compound also blocked head-twitches induced by the 5-HT(2A/2C) receptor agonist 2,5-dimethoxy-4-iodoamphetamine (DOI). Contractions of guinea pig ileum induced by the 5-HT3 receptor agonist 2-methyl-5-HT were prevented by CSP-2503. Moreover, it reduced the bradycardia reflex induced by 2-methyl-5-HT in anaesthetized rats. In the light/dark box and social interaction tests, CSP-2503 presented anxiolytic activity, an action shared by 5-HT1 agonists and 5-HT3 antagonists. Taken together, these results suggest that CSP-2503 is a new 5-HT1 receptor agonist with 5-HT2A and 5-HT3)receptor antagonist activities that might be useful in a number of conditions associated with anxiety.

3,4-Dihydroxyphenylacetic Acid↗

PubMed2004

Antiallodynic effects of intrathecally administered 5-HT(2C) receptor agonists in rats with nerve injury.

Intrathecal administration of serotonin type 2 (5-HT(2)) receptor agonists, alpha-methyl-5-hydroxytryptamine maleate (alpha-m-5-HT) or (+/-)-1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane hydrochloride (DOI), produces antiallodynic effects in a rat model of neuropathic pain. In the present study, we examined the antiallodynic effects of intrathecally administered agents which are selective for 5-HT(2C) receptors. Allodynia was produced by tight ligation of the left L5 and L6 spinal nerves, and was measured by applying von Frey filaments to the left hindpaw. Administration of the 5-HT(2C) receptor agonist, 6-chloro-2-(1-piperazinyl)-pyrazine (MK212; 3-100 microg), 1-(m-chlorophenyl)-piperazine (mCPP; 30-300 microg), or 1-(m-trifluoromethylphenyl)-piperazine (TFMPP; 30-300 microg), produced antiallodynic effects in a dose-dependent manner with no associated motor weakness. The ED(50) values of MK212, mCPP, and TFMPP were 39.2, 119.9, and 191.9 microg, respectively. Intrathecal pretreatment with the selective 5-HT(2C) receptor antagonist RS-102221 (30 microg) diminished the effects of the highest doses of 5-HT(2C) receptor agonists. The preferential 5-HT(2A) receptor antagonist ketanserin (30 microg) did not reverse the effects. In contrast to 5-HT(2C) receptor agonists, the antiallodynic effects of intrathecally administered alpha-m-5-HT (30 microg) and DOI (100 microg) were reversed by ketanserin, but not by RS-102221. These results indicate that 5-HT(2C) receptors have a role in spinal inhibition of neuropathic pain, and the effects produced by intrathecal administration of 5-HT(2C) receptor agonists are mediated by a mechanism different from that of alpha-m-5-HT or DOI, which seem to produce their effects through 5-HT(2A) receptors.

Amphetamines↗

PubMed1998

Lipopolysaccharide inhibition of rat hepatic microsomal epoxide hydrolase and glutathione S-transferase gene expression irrespective of nuclear factor-kappaB activation.

Lipopolysaccharide (LPS) is an endotoxin involved in septic shock syndrome and potentiates toxicant-induced liver injury. The effects of LPS on the constitutive and inducible expression of hepatic microsomal epoxide hydrolase (mEH) and glutathione S-transferase (GST) genes were studied in rats. Northern blot analysis showed that treatment of rats with LPS caused suppression in mEH and GST gene expression. The mEH mRNA level was decreased in a time-dependent manner following a single dose of LPS (1 mg/kg, i.v.), resulting in levels of 52%, 22%, 17%, and 94% of those in untreated animals at 2, 6, 12, and 24 hr, respectively. The levels of rGSTA2 and rGSTA3 mRNA were suppressed in response to an LPS injection to the similar extents as observed in mEH mRNA, whereas rGSTM1 and rGSTM2 mRNA levels were less affected. LPS inhibited mEH gene expression at the doses of 1 microg or greater. Whereas treatment of rats with allyl disulfide (ADS), oltipraz (OZ) or pyrazine (PZ) at the dose of 50 mg/kg caused increases in the mEH mRNA level at 12 hr, a concomitant LPS injection (1 mg/kg) resulted in 80%-95% suppression of the inducible gene expression. The inducible rGSTA2, rGSTA3, rGSTM1, and rGSTM2 mRNA levels were also 50%-90% decreased at 12 hr after LPS treatment, with the relative change in rGSTA being greater than that in rGSTM. Three consecutive daily treatments with LPS (10 microg/kg/day) resulted in significant decreases of the constitutive and PZ (50 mg/kg/day, i.p. for 3 days)-inducible mEH and GST mRNA levels, which were consistent with those in the protein levels. Gel shift retardation analysis showed that LPS substantially activated the hepatic nuclear p65/p50 nuclear factor-kappaB (NF-kappaB) complex with the maximal effect observed at 1 hr at the doses of 1 microg/kg or greater. LPS-induced activation of nuclear NF-kappaB (1 microg/kg, i.v.) failed to be inhibited by concomitant treatment with the mEH and GST inducers, including ADS (300 mg/kg, p.o.), OZ (300 mg/kg, p.o.), and PZ (300 mg/kg, i.p.), indicating that NF-kappaB activation was not required for suppression of the gene expression by LPS. In contrast, GdCl3, an inhibitor of mEH and GST expression, inhibited LPS-induced activation of the p65/p50 NF-kappaB. These gel shift analyses provided evidence that LPS-induced activation of the NF-kappaB was not responsible for alterations in the gene expression. In summary, the results of this research demonstrate that LPS effectively inhibits constitutive and inducible mEH and GST expression with decreases in their mRNA levels, and that LPS suppression in the expression of the detoxifying enzymes is not mediated with its activation of NF-kappaB.

Animals↗

PubMed1998

Serotonin 5-HT2C agonists selectively inhibit morphine-induced dopamine efflux in the nucleus accumbens.

In vivo microdialysis was used to compare the effects of serotonergic drugs on morphine- and cocaine-induced increases in extracellular dopamine (DA) concentrations in the rat nucleus accumbens (NAc). Systemic administration of the 5-HT2A/2C agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) (2.5 mg/kg, s.c. ) prevented the increase in extracellular DA in the NAc produced by morphine (5 mg/kg, i.p.). In contrast, this dose of DOI had no effect on the ability of cocaine (10 mg/kg, i.p.) to increase extracellular DA concentrations in the NAc. A 5-HT2C selective agonist, 6-chloro-2-[1-piperazinyl]-pyrazine (MK-212, 5 mg/kg, s.c.) also inhibited morphine-induced increases in extracellular DA concentrations in the NAc. Pretreatment of rats with the selective 5-HT2A antagonist, amperozide, had no effect on morphine-induced elevation of NAc DA concentrations. In order to determine if inhibition of the firing of 5-HT neurons contributes to the serotonin agonist-mediated inhibition of morphine-induced accumbens DA release, rats were pretreated with the 5-HT1A agonist, 8-OHDPAT. At a dose of 100 microg/kg (sc), 8-OHDPAT did not interfere with morphine's ability to increase DA concentrations in the NAc. These results suggest that the activation of 5-HT2C receptors selectively inhibits morphine-induced DA release in the NAc in a manner which is independent of the inhibition of 5-HT neurons.

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