Biomedical subjects

Stefania Ruiu

Publications and source records attributed to Stefania Ruiu.

At least 19 recordsLinked to original sources

PubMed2006

Tricyclic pyrazoles. 4. Synthesis and biological evaluation of analogues of the robust and selective CB2 cannabinoid ligand 1-(2',4'-dichlorophenyl)-6-methyl-N-piperidin-1-yl-1,4-dihydroindeno[1,2-c]pyrazole-3-carboxamide.

New analogues (2a-p) of the previously reported CB(2) ligands 6-methyl- and 6-chloro-1-(2',4'-dichlorophenyl)-N-piperidin-1-yl-1,4-dihydroindeno[1,2-c]pyrazole-3-carboxamides (1a,b) have been synthesized and evaluated for cannabinoid receptor affinity. One example, 1-(2',4'-dichlorophenyl)-6-methyl-N-cyclohexyilamine-1,4-dihydroindeno[1,2-c] pyrazole-3-carboxamide (2a) was shown to have single digit nanomolar affinity for cannabinoid CB(2) receptors. Furthermore, compounds 2a and 2b, as well as lead structures 1a,b, were also shown to be agonist in an in vitro model based on human promyelocytic leukemia HL-60 cells.

HL-60 Cells↗

PubMed2005

Tricyclic pyrazoles. 3. Synthesis, biological evaluation, and molecular modeling of analogues of the cannabinoid antagonist 8-chloro-1-(2',4'-dichlorophenyl)-N-piperidin-1-yl-1,4,5,6-tetrahydrobenzo[6,7]cyclohepta[1,2-c]pyrazole-3-carboxamide.

A series of analogues of 8-chloro-1-(2',4'-dichlorophenyl)-N-piperidin-1-yl-1,4,5,6-tetrahydrobenzo[6,7]cyclohepta[1,2-c]pyrazole-3-carboxamide 4a (NESS 0327) (Ruiu, S.; Pinna, G. A.; Marchese, G.; Mussinu, J. M.; Saba, P.; Tambaro, S.; Casti, P.; Vargiu, R.; Pani, L. Synthesis and Characterization of NESS 0327: A Novel Putative Antagonist of CB1 Cannabinoid Receptor. J. Pharmacol. Exp. Ther. 2003, 306, 363-370) was synthesized and evaluated for their affinity to cannabinoid receptors. Depending on the chemical modification of the lead structure that was chosen, compounds 4b, 4c, 4i, 4l, and 4m still proved to be potent binders of the CB1 receptor. Moreover, several analogues (4c, 4d, 4e, and 4m) demonstrated superior CB2 receptor binding affinities compared to the parent ligand. Compounds 4b, 4c, 4i, and 4l displayed the most promising pharmacological profiles, having the highest selectivity for CB1 receptors with Ki(CB2) to Ki(CB1) ratios of 11,250, 2000, 3330 and 4625, respectively. Compound 4c increased the intestinal propulsion in mice and antagonized the effect induced by the CB1 receptor agonist WIN 55,212-2. Finally, molecular modeling studies were carried out on a set of tricyclic pyrazoles (2a-4a) and on rimonabant 1 (SR141716A), indicating that high CB1 receptors affinities were consistent for the tricyclic derivatives, both with a nonplanar geometry of the tricyclic cores and with a precise orientation of the substituent (chlorine) on this ring system.

Animals↗

PubMed2005

Modulation of ATP-mediated contractions of the rat vas deferens through presynaptic cannabinoid receptors.

The effect of R-(+)-[2,3-dihydro-5-methyl-3-[(morpholiny)methyl]pyrolol[1,2,3-de]-1,4-benzoxazin-yl]-(1-naphthalenyl)methanone mesylate (WIN 55,212-2; a cannabinoid receptor agonist) was investigated on contractions of the bisected (epididymal and prostatic portions) rat vas deferens to assess the role of cannabinoid receptors in sympathetic ATP neurotransmission. WIN 55,212-2 inhibited the electrically induced contractions in both portions of the rat vas deferens. In the presence of the alpha1-adrenoreceptor antagonist prazosin, electrical stimulation produces a contraction mediated exclusively by ATP. In this condition, WIN 55,212-2 in the prostatic portion elicited a concentration-dependent inhibition that was antagonized by N-piperidinyl-[8-chloro-1-(2,4-dichlorophenyl)-1,4,5,6-tetrahydrobenzo[6,7]cyclohepta[1,2-c]pyrazole-3-carboxamide] (NESS 0327), a selective cannabinoid CB1 receptor antagonist. NESS 0327 caused a parallel dextral displacement of the WIN 55,212-2 concentration-response curve. It is suggested that activation of pre-junctional cannabinoid receptors on sympathetic nerves of the vas deferens modulates ATP neurotransmission.

Adenosine Triphosphate↗

PubMed2005

Tricyclic pyrazoles. Part 2: Synthesis and biological evaluation of novel 4,5-dihydro-1H-benzo[g]indazole-based ligands for cannabinoid receptors.

A series of 4,5-dihydro-1H-benzo[g]indazole-3-carboxamides (2a-k) as analogues of the previously reported CB(2) ligands 6-chloro- and 6-methyl-1-(2',4'-dichlorophenyl)-N-piperidin-1-yl-1,4-dihydroindeno[1,2-c]pyrazole-3-carboxamides (1a,b) was synthesized and their affinity and selectivity towards CB(1) and CB(2) receptors were evaluated. Several of the new compounds (2a,b,c,d and i) exhibited CB(1) affinity in the nanomolar range with moderate or negligible affinity towards CB(2) receptors. Compounds 2a and c increased intestinal propulsion in mouse. Their pro-kinetic effects were reversed by the reference CB agonist CP-55,940. Consequently, in vivo CB(1) antagonistic activity was highlighted for these compounds.

Animals↗

PubMed2004

Evaluation of tamsulosin and alfuzosin activity in the rat vas deferens: relevance to ejaculation delays.

The effect of two alpha-adrenergic receptor antagonists widely employed in the therapy of benign prostatic hyperplasia, tamsulosin [(-)-(R)-5-[2-[[2-(0-ethoxyphenoxy) ethyl]amino]propyl]-2-methoxybenzenesulfonamide] and alfuzosin [(+/-)-N-[3-[(4-amino-6,7-dimethoxy-2-quinazolinyl) methylamino]propyl] tetrahydro-2-furancarboxamide], was investigated in the rat vas deferens. Because several clinical studies have shown that tamsulosin causes ejaculatory disorders, this study also evaluated the possible mechanisms implicated in these disorders by comparing the effect of tamsulosin with that of alfuzosin. Tamsulosin competitively antagonized the contractions induced by noradrenaline in vitro in the epididymal portion of the vas deferens with a potency pA(2) value of 9.2 +/- 0.8. In the prostatic portion, tamsulosin increased the amplitude of intermittent spikes induced by exogenous noradrenaline (100-1000 microM). In both portions of the vas deferens, alfuzosin behaved as an alpha-adrenergic antagonist blocking the contractions induced by exogenous noradrenaline without altering spikes. The administration of tamsulosin (3 microg/kg i.v.) significantly reduced the contractions evoked by electrical pulses in the epididymal portion, whereas it increased those produced in the prostatic portion. Intravenous tamsulosin antagonized the contraction produced by exogenous noradrenaline, whereas alfuzosin administration (10 microg/kg i.v.) did not change the electrically induced contractions in both portions of the rat vas deferens and did not antagonize the contractions produced by exogenous noradrenaline. The fact that tamsulosin unusually enhances noradrenaline-induced intermittent spike contractions and nerve stimulation-induced twitches in the prostatic portions might be linked to its greater propensity to cause sexual dysfunctions.

Adrenergic alpha-Antagonists↗

PubMed2004

Synthesis and biological evaluation of 1,8-naphthyridin-4(1H)-on-3-carboxamide derivatives as new ligands of cannabinoid receptors.

Cannabinoid receptors have been studied extensively in view of their potential functional role in several physiological and pathological processes. For this reason, the search for new potent, selective ligands for subtype CB receptors, CB(1) and CB(2), is still of great importance, in order to investigate their role in various physiological functions. The present study describes the synthesis and the biological properties of a series of 1,8-naphthyridine derivatives, characterised by the presence of some important structural requirements exhibited by other classes of cannabinoid ligands, such as an aliphatic or aromatic carboxamide group in position 3, and an alkyl or arylalkyl substituent in position 1. These compounds were assayed for binding both to the brain and to peripheral cannabinoid receptors (CB(1) and CB(2)). The results obtained indicate that the naphthyridine derivatives examined possess a greater affinity for the CB(2) receptor than for the CB(1) receptor. In particular, derivatives 6a and 7a possess an appreciable affinity for the CB(2) receptor, with K(i) values of 5.5 and 8.0 nM respectively; also compounds 4a, 5a and 8a exhibit a good CB(2) affinity, with K(i) values in the range of 10-44 nM. Furthermore, compounds 3g-i and 18 revealed a good CB(2) selectivity, with a CB(1)/CB(2) ratio >20.

Animals↗

PubMed2004

The cerebellar GABAA alpha6 subunit is differentially modulated by chronic ethanol exposure in normal (R100R) and mutated (Q100Q) sNP rats.

Sardinian alcohol non-preferring (sNP) rats carry a point mutation (R100Q) in the cerebellar expressed GABAA receptor alpha6 subunit gene, leading to a higher sensitivity to ethanol and diazepam. The role of the alpha6 subunit gene cluster in the ethanol non-preferring phenotype was here investigated by measuring the levels of alpha1, alpha6 and gamma2 peptide in the cerebellum of normal (RR) and mutated (QQ) sNP rats after 2 weeks of chronic ethanol administration. Western blot analysis revealed that the alpha6 subunit is increased in RR sNP rats after chronic ethanol exposure (25.44%+/-8.69 versus control), while it remained unchanged in mutated QQ sNP rats. Interestingly, chronic ethanol administration decreased alpha1 peptide levels in the cerebellum of both rat lines to a similar extent (30.99%+/-6.74 and 27.12%+/-9.83 in RR and QQ rats, respectively), while gamma2 peptide levels remained unchanged. To further correlate the genetic and biochemical difference of the normal and mutated sNP rats with their aversive phenotype, we exposed sNP rats to a protocol of acquisition and maintenance of ethanol drinking. QQ sNP rats drank less ethanol than RR rats during the acquisition phase, but such difference was lost during the maintenance phase. These data may contribute to elucidating the mechanisms of alcohol avoidance in rat lines selected for this behavior when exposed to ethanol solution.

Alcoholism↗

PubMed2004

Haloperidol versus risperidone on rat "early onset" vacuous chewing.

Similarly to acute rat catalepsy, "early onset" vacuous chewing movements (VCMs) induced by subchronic treatment with antipsychotic have recently been proposed as a model of human extrapyramidal symptoms. In the present study, the propensities of haloperidol and risperidone in inducing rat "early onset" VCMs were compared using doses of the two antipsychotics that acutely induce similar catalepsy. Comparable rat catalepsy states were observed when the effects produced by 0.1, 0.5, and 1mg/kg of haloperidol were compared with those induced by 1, 4, and 10mg/kg of risperidone, respectively. These doses of the two antipsychotics were then administered twice a day for 4 weeks and VCMs scored after 12h, 5 days, or 3 weeks of drug withdrawal. Among the haloperidol-treated groups, only those rats injected with 0.5 and 1mg/kg showed high levels of VCMs after 12h and 5 days of drug withdrawal when compared to vehicle-treated rats, while basal levels of VCMs were reached after 3 weeks from the last injection. High VCMs levels were observed in risperidone-treated rats only at the dose of 10mg/kg and after 12h of drug withdrawal, but not after 5 days or 3 weeks. The present results indicated that haloperidol possessed a much higher propensity to induce rat "early onset" VCMs than risperidone.

Analysis of Variance↗

PubMed2004

Ritanserin counteracts both rat vacuous chewing movements and nigro-striatal tyrosine hydroxylase-immunostaining alterations induced by haloperidol.

The effect of subchronic co-administration of ritanserin (1.5 mg/kg, i.p., twice a day) and haloperidol (1 mg/kg, i.p., twice a day) on rat vacuous chewing movements and on tyrosine hydroxylase-immunostaining was investigated. Ritanserin significantly reduced rat vacuous chewing movements observed following 2, 3 and 4 weeks of haloperidol administration and after 5 days of haloperidol withdrawal. Furthermore, ritanserin prevented the reduction of striatal tyrosine hydroxylase-immunostaining and the shrinkage of nigral dopaminergic cell bodies induced by haloperidol. The present results indicate that ritanserin may possess protective properties on both dopaminergic nigro-striatal neuron alterations and vacuous chewing movements induced by haloperidol, and provide further evidence indicating a possible association between these two haloperidol-induced effects.

Animals↗

PubMed2004

Blockade of neurotensin receptors affects differently hypo-locomotion and catalepsy induced by haloperidol in mice.

Antipsychotic drug treatment increases neurotensin (NT) neurotransmission, and the exogenous administration of NT produces antipsychotic-like effects in rodents. In order to investigate whether "endogenous" NT may act as a natural occurring antipsychotic or may mediate antipsychotic drug activity, the effects of the selective NT receptor antagonists SR 48692 and SR 142948A were analyzed in different behavioural tests of locomotor activity using vehicle, amphetamine, or haloperidol in mice. SR 48692 (0.1-1 mg/kg, i.p.) and SR 142948A (0.03-0.1 mg/kg, i.p.) failed to affect mouse spontaneous locomotor activity and amphetamine-induced (2.5 mg/kg, i.p.) hyper-locomotion. However, SR 48692 (0.1 and 0.3 mg/kg, i.p.) and SR 142948A (0.03 and 0.05 mg/kg, i.p.) significantly alleviated the reduction of locomotor activity elicited by haloperidol (0.01 and 0.04 mg/kg, s.c.) in vehicle- or amphetamine-treated mice. Finally, SR 48692 (0.3 mg/kg, i.p.) and SR 142948A (0.05 and 0.1 mg/kg, i.p.) increased mouse catalepsy produced by haloperidol (0.3 mg/kg, s.c.). The present results indicate that while endogenous NT is not involved in the modulation of either mouse spontaneous locomotor activity or amphetamine-induced hyper-locomotion, it might act by enhancing the therapeutic effects of haloperidol and by attenuating the extrapyramidal side effects elicited by this antipsychotic.

Adamantane↗

PubMed2003

Synthesis of novel diazatricyclodecanes (DTDs). Effects of structural variation at the C3' allyl end and at the phenyl ring of the cinnamyl chain on mu-receptor affinity and opioid antinociception.

Two series of analogues of 9-propionyl-10-cinnamyl-9,10-diazatricyclo[4.2.1.1(2,5)]decane (1a) and 2-propionyl-7-cinnamyl-2,7-diazatricyclo[4.4.0.0(3,8)]decane (2a), in which the cinnamyl moiety was replaced by various aralkenyl chains, 1b-l and 2b-l, respectively, have been synthesized and evaluated for their ability to bind to the opioid mu-, delta- and kappa-receptors. The binding data indicated that compounds 1b,d,e,h and 2b,d,e,f,h,i showed a mu-affinity in the low nanomolar range with moderate or negligible affinity towards delta- and kappa-receptors. Selected DTDs, the pairs 1,2b, 1,2e and 1,2h, were also evaluated for analgesic effect. In the hot plate test, only 1b given ip was found to have similar opioid antinociception and chronic tolerance as morphine.

Analgesics, Opioid↗

PubMed2003

Haloperidol, but not clozapine, produces dramatic catalepsy in delta9-THC-treated rats: possible clinical implications.

The effect on rat catalepsy induced by Delta9-tetrahydrocannabinol (Delta9-THC) in association with haloperidol (HP) or clozapine (CLOZ) administration was investigated. Delta9-THC dose-dependently increased HP (0.05-1 mg kg-1, s.c.)-induced rat catalepsy, while no catalepsy was observed after CLOZ (1-20 mg kg-1, s.c.) or Delta9-THC+CLOZ administration. The CB1 antagonist SR141716A (0.5-5 mg kg-1, i.p.) reversed the increase mediated by Delta9-THC on HP-induced catalepsy. The D2 agonist quinpirole completely reversed the catalepsy induced by both HP and HP+Delta9-THC; however, higher doses of quinpirole were needed in the presence of Delta9-THC. The M1 antagonist scopolamine and alpha2 antagonist yohimbine were able to reduce the catalepsy induced by HP and HP+Delta9-THC in a similar manner. CLOZ and the 5-HT2A/2C antagonists ritanserin, RS102221 and SB242084 were more effective in antagonizing HP than HP+Delta9-THC-induced catalepsy.7 HP and CLOZ failed to inhibit in vitro [3H]CP-55,940 binding, while Delta9-THC and SR141716A did not show an appreciable affinity for the D2 receptor. It was suggested that the different effects on rat catalepsy induced by Delta9-THC following HP or CLOZ administration may depend on the receptor-binding profiles of the two antipsychotics. The preferential use of CLOZ rather than HP in the treatment of psychotic symptoms in cannabis abusers was discussed.

Animals↗

PubMed2003

Characterization of wild-type (R100R) and mutated (Q100Q) GABAA alpha 6 subunit in Sardinian alcohol non-preferring rats (sNP).

Sardinian alcohol non-preferring (sNP) rats, selected for their low ethanol preference and consumption, carry a point mutation (R100Q) in the gene coding for GABA(A) receptor alpha(6) subunit, which becomes more sensitive to diazepam-evoked GABA currents. We performed binding studies in the cerebellum of normal (RR) and mutated (QQ) sNP rats using [3H]Ro 15-4513, an inverse agonist for the benzodiazepine site which binds both diazepam insensitive and diazepam sensitive sites. Saturation curves performed on cerebellar membrane from genotyped rats indicated an higher affinity of [3H]Ro 15-4513 for GABA(A) receptors in QQ with respect to RR rats (K(d) values 4.0+/-0.67 and 6.24+/-0.95 nM, respectively), with similar B(max) values (3.5+/-0.25 and 3.9+/-0.39 pmol/mg protein, respectively). Diazepam displacement curves showed a two component model for both genotypes, with similar K(i1) values for QQ and RR (3.6+/-0.62 and 4.9+/-0.33 nM, respectively). In QQ rats diazepam is able to completely displace [3H]Ro 15-4513 (K(i2)=1.48+/-0.27 microM), while in RR rats the diazepam sensitive sites are still present (K(i2)>10 microM). The basal mRNA and protein expression level of the alpha(6) subunit were similar in RR and QQ rats. The electrophysiological profile of oocytes of Xenopus laevis injected with cerebellar synaptosomes showed that ethanol positively modulated GABA-evoked currents significantly more in QQ than in RR rats. These data contribute to the characterization of the function of GABA(A) alpha(6) subunit and its involvement in determining alcohol related behavior.

Alcohol Drinking↗

PubMed2003

Synthesis and characterization of NESS 0327: a novel putative antagonist of the CB1 cannabinoid receptor.

The compound N-piperidinyl-[8-chloro-1-(2,4-dichlorophenyl)-1,4,5,6-tetrahydrobenzo [6,7]cyclohepta[1,2-c]pyrazole-3-carboxamide] (NESS 0327) was synthesized and evaluated for binding affinity toward cannabinoid CB1 and CB2 receptor. NESS 0327 exhibited a stronger selectivity for CB1 receptor compared with N-piperidinyl-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (SR 141716A), showing a much higher affinity for CB1 receptor (Ki = 350 +/- 5 fM and 1.8 +/- 0.075 nM, respectively) and a higher affinity for the CB2 receptor (Ki = 21 +/- 0.5 nM and 514 +/- 30 nM, respectively). Affinity ratios demonstrated that NESS 0327 was more than 60,000-fold selective for the CB1 receptor, whereas SR 141716A only 285-fold. NESS 0327 alone did not produce concentration-dependent stimulation of guanosine 5'-O-(3-[35S]thio)-triphosphate ([35S]GTPgammaS) binding in rat cerebella membranes. Conversely, NESS 0327 antagonized [R(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrolol [1,2,3-de]-1,4-benzoxazin-yl]-(1-naphthalenyl)methanone mesylate] (WIN 55,212-2)-stimulated [35S]GTPgammaS binding. In functional assay, NESS 0327 antagonized the inhibitory effects of WIN 55,212-2 on electrically evoked contractions in mouse isolated vas deferens preparations with pA2 value of 12.46 +/- 0.23. In vivo studies indicated that NESS 0327 antagonized the antinociceptive effect produced by WIN 55,212-2 (2 mg/kg s.c.) in both tail-flick (ID50 = 0.042 +/- 0.01 mg/kg i.p.) and hot-plate test (ID50 = 0.018 +/- 0.006 mg/kg i.p.). These results indicated that NESS 0327 is a novel cannabinoid antagonist with high selectivity for the cannabinoid CB1 receptor.

Animals↗

PubMed2003

Tricyclic pyrazoles. Part 1: synthesis and biological evaluation of novel 1,4-dihydroindeno[1,2-c]pyrazol-based ligands for CB1and CB2 cannabinoid receptors.

Cannabinoids receptors, cellular elements of the endocannabinoid system, have been the focus of extensive studies because of their potential functional role in several important physiological and pathological processes. To further evaluate the properties of CB receptors, especially CB(1) and CB(2) subtypes, we have designed, using SR141716A as a benchmark, a new series of rigid 1-aryl-1,4-dihydroindeno[1,2-c]pyrazole-3-carboxamides. Compounds 1 were synthesized from substituted 1-aryl-1,4-dihydroindeno[1,2-c]pyrazole-3-carboxylic acids and requisite amines. The various analogues were assayed for binding both to the brain and peripheral cannabinoid receptors (CB(1) and CB(2)). Seven of the new compounds displayed very high in vitro CB(2) binding affinities, especially 1a, 1b, 1c, 1e, 1g, 1h and 1j which showed K(i) values of 0.34, 0.225, 0.27, 0.23, 0.385, 0.037 and 0.9 nM, respectively. Compounds 1a, 1b, 1c and 1h showed the highest selectivity for CB(2) receptor with K(i)(CB(1)) to K(i)(CB(2)) ratios of 6029, 5635, 5814 and 9810, respectively. Noticeably, 1h exhibited the highest affinity and selectivity for CB(2) receptors.

Amines↗

PubMed2003

Differential distribution of functional cannabinoid CB1 receptors in the mouse gastroenteric tract.

Recently, the gastrointestinal pharmacology of cannabinoid CB(1) receptors has been extensively explored. We employed western blotting and immunohistochemistry techniques to study the distribution of the cannabinoid CB(1) receptor protein in the mouse gastroenteric tract. The cannabinoid CB(1) receptor peptide was detected by western blotting only in its glycosylated form (63 kDa) with a significant differential distribution. The highest levels of expression were detected in the stomach and in the colon, while the pyloric valve was devoid of any cannabinoid CB(1) receptor protein. The immunohistochemical study showed intense cannabinoid CB(1) receptor immunoreactivity in ganglia subadjacent to the gastric epithelium and in the smooth muscle layers of both the small and large intestine. Only the small intestine showed (-)-3-[2-hydroxyl-4-(1,1-dimethylheptyl)-phenyl]-4-(3-hydroxylpropyl) cyclohexan-1-ol) ([3H]CP 55,940) specific binding (27%). These receptors mediated pharmacologically significant effects since the cannabinoid CB(1) receptor agonist R(-)-7-hydroxy-delta-6-tetra-hydrocannabinol-dimethylheptyl (HU 210) dose dependently inhibited gastrointestinal transit up to 70%, while the cannabinoid CB(1) receptor antagonist N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methylpyrazole-3-carboxamide (SR 141716A) increased gastrointestinal transit. Moreover, the dose of 0.3 microg/kg of HU 210, devoid per se of any activity on mouse intestinal propulsion, blocked the increased gastroenteric transit induced by the cannabinoid CB(1) antagonist SR 141716A.

Animals↗

PubMed2003

In vitro evidence for the presence of [3H]-haloperidol uptake in rat brain.

1 The neuroleptic [(3)H]-haloperidol (HP) was taken up in synaptosomes prepared from rat brain, in a temperature-, sodium ion-, and energy-dependent process. 2 The highest concentration of uptake sites (V(max)=2.37 pmol mg(-1) protein min(-1)) was in the striatum with the other brain areas displaying lower (by 50-70%) values. 3 The affinity values (K(m) approximately equal to 40 nM) were similar in all brain areas considered. 4 The pharmacological characterization did not indicate a well-defined group of inhibitors, which suggested that HP might not use a transporter for recognized neurotransmitters. 5 The HP metabolites tested, including HPTP, were competitive inhibitors of [(3)H]-HP uptake, an indirect indication that they may actively enter the striatal nerve endings through the same carrier. 6 Since the uptake process was partially affected by the incubation of [(3)H]-HP in the presence of several antagonists of HP-transforming cytochrome P450 isoforms, the binding of HP at some enzyme sites inside the synaptosome cannot be excluded. 7 In conclusion, the present results suggest that HP may be actively transported in the rat brain.

Animals↗

PubMed2002

Effect of the amisulpride isomers on rat prolactinemia.

The effects on rat serum prolactin level of the two isomers constituting the racemic form of amisulpride were compared. (S-)-amisulpride induced hyperprolactinemia at lower doses (ED(50) = 0.09 +/- 0.01 mg/kg) than racemic- (ED(50) = 0.24 +/- 0.03 mg/kg) and (R+)-amisulpride (ED(50) = 4.13 +/- 0.05 mg/kg), in accord with their affinities for pituitary dopamine D(2) receptor (K(i) = 3.8 +/- 0.2, 6.4 +/- 0.2 and 143.3 +/- 2.3 nM, respectively). At doses twice the ED(50), (S-)-amisulpride produced a maximal increase in prolactin level similar to that of the racemic form (403 +/- 21% and 425 +/- 15%, respectively), but higher than that of (R+)-amisulpride (198 +/- 8%). These results suggest that the hyperprolactinemia induced by the racemic-amisulpride is mostly due to its (S-)-isomer.

Amisulpride↗