ro-60-0175 and 1-(3-chlorophenyl)piperazine

The role of 5-HT2C receptors (5-HT2CRs) in the regulation of anxiety has been widely acknowledged. However, conflicting results have been reported on whether stimulation of these receptors increases or decreases anxiety. We here investigated the role of 5-HT2CRs of the dorsal hippocampus (DH) in the mediation of anxiety- or panic-associated defensive behaviors and in the anxiolytic effect of the tricyclic antidepressant imipramine. In the Vogel conflict test, administration of the mixed 5-HT2CR agonist mCPP into the DH of male Wistar rats was anxiogenic, whereas infusions of the more selective agonists MK-212 and RO-600175 were anxiolytic. The 5-HT2CR antagonist SB-242084, on the other hand, was anxiogenic. A sub-effective dose of this antagonist blocked the anxiolytic effect of RO-600175, but not the increase in anxiety observed with mCPP, indicating that the latter effect was not due to 5-HT2CR activation. In full agreement with these findings, MK-212 and RO-600175 in the DH also inhibited inhibitory avoidance acquisition in the elevated T-maze, whereas SB-242084 caused the opposite effect. None of these drugs interfered with escape expression in this test, which has been associated with panic. Chronic administration of imipramine (15 mg/kg, ip, 21 days) caused an anxiolytic effect in the elevated T-maze and light-dark transition tests, which was not blocked by previous infusion of SB-242084 into the DH. Therefore, facilitation of 5-HT2CR-mediated neurotransmission in the DH decreases the expression of anxiety-, but not panic-related defensive behaviors. This mechanism, however, is not involved in the anxiolytic effect caused by imipramine.

Topics: Aminopyridines; Animals; Anti-Anxiety Agents; Anxiety; Avoidance Learning; Ethylamines; Hippocampus; Imipramine; Indoles; Male; Maze Learning; Microinjections; Panic; Piperazines; Punishment; Pyrazines; Rats; Receptor, Serotonin, 5-HT2C; Serotonin 5-HT2 Receptor Agonists

Accumulating evidence indicates that the serotonin system modulates the behavioral and neurochemical effects of cocaine, but the receptor subtypes mediating these effects remain unknown. Recent studies have demonstrated that pharmacological activation of the serotonin 2C receptor (5-HT(2C)R) attenuates the behavioral and neurochemical effects of cocaine in rodents, but such compounds have not been systematically evaluated in nonhuman primates. The present experiments sought to determine the impact of pretreatment with the preferential 5-HT(2C)R agonist m-chlorophenylpiperazine (mCPP) and the selective 5-HT(2C)R agonist Ro 60-0175 [(α-S)-6-chloro-5-fluoro-α-methyl-1H-indole-1-ethanamine fumarate] on the behavioral and neurochemical effects of cocaine in squirrel monkeys. In subjects trained to lever-press according to a 300-s fixed-interval schedule of stimulus termination, pretreatment with either 5-HT(2C)R agonist dose-dependently and insurmountably attenuated the behavioral stimulant effects of cocaine. In subjects trained to self-administer cocaine, both compounds dose-dependently and insurmountably attenuated cocaine-induced reinstatement of previously extinguished responding in an antagonist-reversible manner, and the selective agonist Ro 60-0175 also attenuated the reinforcing effects of cocaine during ongoing cocaine self-administration. It is noteworthy that the selective agonist Ro 60-0175 exhibited behavioral specificity because it did not significantly alter nondrug-maintained responding. Finally, in vivo microdialysis studies revealed that pretreatment with Ro 60-0175 caused a reduction of cocaine-induced dopamine increases within the nucleus accumbens, but not the caudate nucleus. These results suggest that 5-HT(2C)R agonists functionally antagonize the behavioral effects of cocaine in nonhuman primates, possibly via a selective modulation of cocaine-induced dopamine increases within the mesolimbic dopamine system and may therefore represent a novel class of pharmacotherapeutics for the treatment of cocaine abuse.

Topics: Animals; Behavior, Animal; Caudate Nucleus; Cocaine; Dopamine; Drug Interactions; Ethylamines; Indoles; Male; Microdialysis; Nucleus Accumbens; Piperazines; Receptor, Serotonin, 5-HT2C; Saimiri; Self Administration; Serotonin 5-HT2 Receptor Agonists

The serotonin 5-HT2C receptor (5-HT2CR) is expressed in amygdala, a region involved in anxiety and fear responses and implicated in the pathogenesis of several psychiatric disorders such as acute anxiety and post traumatic stress disorder. In humans and in rodent models, there is evidence of both anxiogenic and anxiolytic actions of 5-HT2C ligands. In this study, we determined the responsiveness of 5-HT2CR in serotonin transporter (SERT) knockout (-/-) mice, a model characterized by increased anxiety-like and stress-responsive behaviors.. In the three-chamber social interaction test, the 5-HT2B/2C agonist mCPP decreased sociability and sniffing in SERT wildtype (+/+) mice, both indicative of the well-documented anxiogenic effect of mCPP. This 5-HT2C-mediated response was absent in SERT-/- mice. Likewise, in the open field test, the selective 5-HT2C agonist RO 60-0175 induced an anxiogenic response in SERT+/+ mice, but not in SERT-/- mice. Since 5-HT2CR pre-mRNA is adenosine-to-inosine (A-to-I) edited, we also evaluated the 5-HT2CR RNA editing profiles of SERT+/+ and SERT-/- mice in amygdala. Compared to SERT+/+ mice, SERT-/- mice showed a decrease in less edited, highly functional 5-HT2C isoforms, and an increase in more edited isoforms with reduced signaling efficiency.. These results indicate that the 5-HT2CR in the amygdala of SERT-/- mice has increased RNA editing, which could explain, at least in part, the decreased behavioral responses to 5-HT2C agonists in SERT-/- mice. These alterations in 5-HT2CR in amygdala may be relevant to humans with SERT polymorphisms that alter SERT expression, function, and emotional behaviors.

Topics: Amygdala; Animals; Anxiety; Behavior, Animal; Ethylamines; Indoles; Interpersonal Relations; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Piperazines; Receptor, Serotonin, 5-HT2C; RNA Editing; RNA Precursors; Serotonin 5-HT2 Receptor Agonists; Serotonin Plasma Membrane Transport Proteins

Stress is known to activate the central 5-hydroxytryptamine (5-HT) system, and this is probably part of a coping response involving several 5-HT receptors. Although 5-HT(2C) receptors are well known to be implicated in anxiety, their participation in stress-induced changes had not been investigated in parallel at both behavioral and neurochemical levels. We show here that the preferential 5-HT(2C) receptor agonist, m-chlorophenylpiperazine, as well as restraint stress increased anxiety in the mouse social interaction test. The selective 5-HT(2C) receptor antagonist, SB 242,084, prevented both of these anxiogenic effects. Restraint stress increased 5-HT turnover in various brain areas, and this effect was prevented by the 5-HT(2B/2C) receptor agonist RO 60-0175 (1 mg/kg), but not the preferential 5-HT(2A) agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (1 mg/kg), and in contrast potentiated by SB 242,084 (1 mg/kg), which also blocked the effect of RO 60-0175. Using microdialysis, RO 60-0175 was shown to inhibit cortical 5-HT overflow in stressed mice when 5-HT reuptake was blocked locally. Chronic paroxetine prevented both the anxiogenic effect of m-chlorophenylpiperazine and the inhibitory effect of RO 60-0175 on locomotion and stress-induced increase in 5-HT turnover. The anxiolytic action of chronic paroxetine might be associated with an enhancement of 5-HT neurotransmission caused by a decreased 5-HT(2C) receptor-mediated inhibition of stress-induced increase in 5-HT release.

Topics: Amphetamines; Analysis of Variance; Animals; Antidepressive Agents, Second-Generation; Behavior, Animal; Brain; Ethylamines; Extracellular Fluid; Gene Expression Regulation; Indoles; Interpersonal Relations; Male; Mice; Mice, Inbred C57BL; Motor Activity; Paroxetine; Piperazines; Receptor, Serotonin, 5-HT2C; Serotonin; Serotonin Receptor Agonists; Stress, Psychological

5-HT(2C) receptor agonists have considerable therapeutic potential, however there is little in vivo data to compare the potency and selectivity of 5-HT(2C) receptor agonists. Since 5-HT(2C) receptor agonists reduce locomotor activity and food intake, changes in these drug-induced behaviours in 5-HT(2C) receptor knockout mice could provide a means to examine receptor selectivity in-vivo. Initially this study compared older 5-HT(2C) agonists mCPP and MK212, to newer, apparently more selective compounds: Ro 60-0175, WAY161503, CP809,101 and lorcaserin (APD356) on motor activity in wild-type, and 5-HT(2C) receptor knockout mice. Two 5-HT(2C) receptor antagonists SB242084 and SDZ SER 082 were also examined. mCPP did not significantly alter activity in wild-type mice, but enhanced activity in knockout animals. MK212 (3 and 10 mg/kg) and Ro 60-0175 (1 and 3 mg/kg) reduced activity in wild-type but not knockout animals. At 10 mg/kg, Ro 60-0175 reduced activity in knockout animals, suggesting loss of 5-HT(2C) receptor selectivity. CP809,101 and lorcaserin reduced activity in wild-type but not knockout mice. In subsequent feeding studies, Ro 60-0175 and lorcaserin reduced food intake in wild-type animals only. Selectivity of effect for mCPP was marginal. The antagonist SB242084 increased activity in wild-type animals but not in knockout mice; SB242084 did not alter feeding in either genotype. SDZ SER 082 reduced activity in both genotypes implying poor selectivity for 5-HT(2C) receptors. The data demonstrate that studying food intake, and particularly motor behaviour, in the 5-HT(2C) receptor knockout mouse is a useful and relatively simple approach for screening 5-HT(2C) receptor ligands in vivo.

Topics: Aminopyridines; Animals; Benzazepines; Dexfenfluramine; Eating; Ethylamines; Feeding Behavior; Indoles; Ligands; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Motor Activity; Naphthyridines; Piperazines; Pyrazines; Quinoxalines; Receptor, Serotonin, 5-HT2C; Serotonin Antagonists; Serotonin Receptor Agonists

Food intake and energy expenditure are the two main determinants of body weight. Given that 5-HT(2C) receptor agonists are reported to have effects on both energy expenditure and food intake, this strongly suggests that 5-HT(2C) receptor agonists have excellent potential for development as antiobesitiy drugs. One important issue in antiobesity drug development is whether the effects of the compound are maintained during chronic drug treatment.. The purpose of the present study was to investigate the effect of repeated oral administration of three 5-HT(2C) receptor agonists, m-chlorophenylpiperazine (mCPP), d(S)-2-(6-chloro-5-fluoroindol-1-yl)-1-methylethylamine (RO60-0175) and (S)-2-(7-ethyl-1H-furo[2,3-g]indazol-1-yl)-1-methylethylamine (YM348), on food intake and energy expenditure in rats.. In the food intake study, mCPP, RO60-0175 and YM348 decreased food intake in a dose-dependent manner on day 1 of administration. On day 14 of repeated administration, the hypophagic effect of YM348 was lost and that of mCPP was reduced. In contrast, the hypophagic effect of RO60-0175 was maintained even after repeated administration. The hypophagic effects of all agonists were significantly inhibited by a 5-HT(2C) receptor antagonist, SB242084. In contrast to the hypophagic effects, no drug tolerance developed with respect to the hyperthermic effects of mCPP, RO60-0175, and YM348. The hyperthermic effects of these drugs were also inhibited by SB242084.. Together, the difference between compounds in their hypophagic effects and the similarity in their hyperthermic effects suggest a diversity in agonists in 5-HT(2C) receptor-mediated weight control in rats.

Topics: Administration, Oral; Aminopyridines; Animals; Appetite Depressants; Dose-Response Relationship, Drug; Drug Interactions; Energy Metabolism; Ethylamines; Feeding Behavior; Indazoles; Indoles; Male; Piperazines; Rats; Rats, Wistar; Serotonin 5-HT2 Receptor Agonists; Weight Loss

Although null mutant ('knockout') mice have provided valuable animal models to complement traditional approaches to psychopharmacology, such animals may also show complex adaptations to the induced mutation. Here we demonstrate that serotonin1B (5-HT1B) receptor knockout (KO) mice show adaptations in serotonin2C (5-HT2C) receptor-mediated functions. They show smaller reductions in food intake and locomotor activity in response to administration of 5-HT2C receptor agonists that are not accounted for by altered drug disposition. These effects are not mimicked by pretreatment of wildtype (WT) mice with a 5-HT1B receptor antagonist showing that they result from a longer term adaptation to the loss of 5-HT1B receptor function and not from a short-term interaction between 5-HT1B- and 5-HT2C-mediated functions. In addition, we show that 5-HT1B receptor KO mice have a lowered hypothalamic c-fos response to the administration of 5-HT2C receptor agonists. These results demonstrate that compensatory adaptations to the constitutive loss of 5-HT1B receptors may be an important determinant of the altered response of 5-HT1B KO mice to a variety of pharmacological challenges.

Topics: Animals; Cell Count; Dose-Response Relationship, Drug; Down-Regulation; Eating; Ethylamines; Hypothalamus; Indoles; Male; Mice; Mice, Knockout; Motor Activity; Piperazines; Proto-Oncogene Proteins c-fos; Receptor, Serotonin, 5-HT1B; Receptor, Serotonin, 5-HT2C; Receptors, Serotonin; Serotonin Agents; Serotonin Receptor Agonists; Time Factors

Direct-acting serotonin (5-HT) receptor agonists increase serum corticosterone in rats by activating receptors of the 5-HT(1A) or the 5-HT(2A/2C) subtypes. While involvement of 5-HT(1A) receptors in activation of the hypothalamic-pituitary-adrenocortical (HPA) axis is clear, the 5-HT(2) receptor subtype--5-HT(2A) or 5-HT(2C)--responsible for activation of the HPA axis by direct-acting 5-HT(2) receptor agonists has been difficult to determine due to the lack of selective pharmacologic agents. Recently, however, 5-HT(2) receptor antagonists with high selectivity for 5-HT(2A) and 5-HT(2C) receptor subtypes have been discovered. The selective 5-HT(2A) receptor antagonist MDL 100,907 and the selective 5-HT(2C) receptor antagonist SB 242084 were used to block the increases in rat serum corticosterone elicited by 5-HT(2) receptor agonists with varying degrees of affinity for 5-HT(2A) and 5-HT(2C) receptors. MDL 100,907 was fully effective in blocking the increases in corticosterone concentrations produced by quipazine, DOI, m-CPP and Ro 60-0175, whereas SB 242084 was ineffective or was only marginally effective. Our findings implicate 5-HT(2A) receptors rather than 5-HT(2C) receptors in mediating increases in rat serum corticosterone produced by direct-acting 5-HT(2) receptor agonists in vivo.

Topics: Aminopyridines; Amphetamines; Animals; Corticosterone; Dose-Response Relationship, Drug; Ethylamines; Fluorobenzenes; Hypothalamo-Hypophyseal System; Indoles; Male; Piperazines; Piperidines; Quipazine; Rats; Rats, Sprague-Dawley; Receptor, Serotonin, 5-HT2A; Receptors, Serotonin; Serotonin Antagonists; Serotonin Receptor Agonists

The studies reported here examined the role of the 5-hydroxytryptamine (5-HT)(2C) receptor subtype in the control of ingestive behaviour in mice. Behavioural satiety sequence (BSS) and food intake measurements were taken, comparing the selective 5-HT(2C) receptor agonist (S)-2-(6-chloro-5-fluoro-indol-l-yl)-l-methylethylamine hydrochloride (Ro 60-0175; 1.0, 3.0 and 10.0 mg/kg) and D-fenfluramine (3.0 mg/kg). Ro 60-0175 produced a dose-dependent decrease in food intake. The effects of Ro 60-0175 (3.0 mg/kg) on the BSS were similar to the hypophagic effects of D-fenfluramine (3.0 mg/kg). In a second experiment, the specific effects on feeding produced by Ro 60-0175 (5.6 mg/kg) were attenuated by pretreatment with the selective 5-HT(2C) receptor antagonist 6-chloro-5-methyl-1-[2(2-methylpyridyl-3-oxy)-pyrid-5-yl carbamoyl] indoline (SB 242084; 0.5 mg/kg). The 5-HT(1B/2C) receptor agonist 1-(m-chlorophenyl)piperazine (mCPP; 3 mg/kg) also produced a substantial decrease in food intake, which was attenuated by SB 242084 (0.5 mg/kg). A dose of the selective 5-HT(1B/1D) antagonist 2'-methyl-4'(5-methyl-[1,2,4]oxadiazol-3-yl)-biphenyl-4-carboxylic acid [4-(5-methoxy-3-(4-methyl-piperazin-1-yl)-phenyl]amide (GR 127935; 3.0 mg/kg) that successfully attenuated the action of the 5-HT(1B) agonist 5-methoxy-3(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole (RU 24969; 5.0 mg/kg) failed to attenuate mCPP-induced hypophagia. These data suggest that Ro 60-0175- and mCPP-induced hypophagia in mice are mediated via activation of 5-HT(2C) receptors and that stimulation of 5-HT(1B) receptors plays only a minor role in mCPP-induced hypophagia.

Topics: Aminopyridines; Animals; Diet; Dose-Response Relationship, Drug; Ethylamines; Feeding Behavior; Indoles; Mice; Oxadiazoles; Piperazines; Receptor, Serotonin, 5-HT1B; Receptor, Serotonin, 5-HT2C; Receptors, Serotonin; Satiety Response; Serotonin Antagonists; Serotonin Receptor Agonists

1. The aim of the study was to compare the effects of 14 day subcutaneous infusion of the 5-HT(2C) receptor agonists, m-chlorophenylpiperazine (mCPP, 12 mg kg(-1) day(-1)) and Ro 60-0175 (36 mg kg(-1) day(-1)) and the 5-HT releasing agent and re-uptake inhibitor, d-fenfluramine (6 mg kg(-1) day(-1)), on food and water intake, body weight gain and locomotion in lean male Lister hooded rats. 2. Chronic infusion of all three drugs significantly reduced food intake and attenuated body weight gain. In contrast, drug infusion did not lead to significant reductions in locomotor activity in animals assessed 2 and 13 days after pump implantation. 3. In a subsequent 14 day study that was designed to identify possible tolerance during days 7 - 14, animals were given a subcutaneous infusion of mCPP (12 mg kg(-1) day(-1)) or d-fenfluramine (6 mg kg(-1) day(-1)) for either 7 or 14 days. During the first 7 days both drugs significantly reduced body weight gain compared to saline-infused controls; however, from day 7 onwards animals withdrawn from drug treatment exhibited an increase in body weight such that by day 14 they were significantly heavier than their 14-day drug-treated counterparts. 4. Both mCPP and d-fenfluramine reduced daily food intake throughout the infusion periods. For 14-day treated animals this hypophagia was marked during the initial week of the study but only minor during the second week. In light of the sustained drug effect on body weight, the data suggest that weight loss by 5-HT(2C) receptor stimulation may be only partly dependent on changes in food consumption and that 5-HT(2C) receptor agonists may have effects on thermogenesis. 5. These data suggest tolerance does not develop to the effects of d-fenfluramine, mCPP and Ro 60-0175 on rat body weight gain.

Topics: Analysis of Variance; Animals; Body Weight; Drinking; Eating; Ethylamines; Fenfluramine; Hypothalamus; Indoles; Infusion Pumps; Motor Activity; Piperazines; Rats; Receptor, Serotonin, 5-HT2C; Receptors, Serotonin; RNA, Messenger; Serotonin Agents; Time Factors

The role of the 5-HT(2C) receptor in mediating active behaviors in the modified rat forced swim test was examined. Three novel selective 5-HT(2C) receptor agonists, WAY 161503 (0.1-3.0 mg/kg), RO 60-0175 (2-20 mg/kg), and RO 60-0332 (20 mg/kg), all decreased immobility and increased swimming, a pattern of behavior similar to that which occurs with the selective serotonin reuptake inhibitor fluoxetine (5-20 mg/kg). However, the prototypical but nonselective 5-HT(2C) receptor agonist m-chlorophenylpiperazine (1-10 mg/kg) increased immobility scores in the forced swim test. The selective 5-HT(2C) receptor antagonist SB 206533 was inactive when given alone (1-20 mg/kg). However, SB 206533 (20 mg/kg) blocked the antidepressant-like effects of both WAY 161503 (1 mg/kg) and fluoxetine (20 mg/kg). The atypical antidepressant (noradrenergic alpha(2) and 5-HT(2C) receptor antagonist) mianserin reduced immobility and increased climbing at 30 mg/kg. At a behaviorally subactive dose (10 mg/kg), mianserin abolished the effects of WAY 161503 (1 mg/kg) on both swimming and immobility scores. Mianserin blocked the effects of fluoxetine (20 mg/kg) on swimming only; mianserin plus fluoxetine reduced immobility and induced a switch to climbing behavior, suggesting activation of noradrenergic transmission. These data exemplify the benefits of using the modified rat forced swim test, which was sensitive to serotonergic compounds and distinguished behavioral changes associated with serotonergic and noradrenergic effects. Taken together, the results strongly implicate a role for 5-HT(2C) receptors in the behavioral effects of antidepressant drugs.

Topics: Animals; Antidepressive Agents; Dose-Response Relationship, Drug; Ethylamines; Fluoxetine; Indoles; Male; Mianserin; Piperazines; Rats; Rats, Sprague-Dawley; Receptor, Serotonin, 5-HT2C; Receptors, Serotonin; Serotonin Receptor Agonists; Swimming

Employing a Fixed-Ratio 10, food-reinforced protocol, rats were trained to recognize the discriminative stimulus (DS) properties of the novel, potent, 5-HT2C agonist, Ro 60-0175 (2.5 mg/kg, i.p.). This schedule generated appropriate drug versus vehicle responding after 50 + 5 training sessions and Ro 60-0175 elicited full (100%) drug selection with an effective dose50 (ED50) of 0.6 mg/kg, i.p.. The 5-HT2C receptor agonists, mCPP and MK 212, fully generalized to Ro 60-0175 with ED50s of 0.8 and 0.4 mg/kg, s.c., respectively, whereas the preferential 5-HT2B agonist, BW 723C86 ( > 10.0 mg/kg, s.c.) and the 5-HT2A agonist, DOI ( > 2.5 mg/kg, s.c.), were ineffective. The 5-HT2A/2B/2C receptor antagonist, mianserin, dose-dependently blocked the DS properties of Ro 60-0175 with an ED50 of 0.7 mg/kg, s.c. This action was mimicked by the novel, 5-HT2B/2C antagonist, SB 206,553 (ED50 = 0.3 mg/kg, s.c.), whereas the selective 5-HT2A antagonist, MDL 100,907 ( > 0.63 mg/kg, s.c.), was ineffective. Further, the selective 5-HT2C antagonist, SB 242,084, dose-dependently and fully blocked drug selection (ED50 = 0.2 mg/kg, i.p.), whereas the selective 5-HT2B antagonist, SB 204,741, was not active ( > 0.63 mg/kg, i.p.). In conclusion, these data demonstrate that Ro 60-0175 generates a robust DS and suggest that activation of 5-HT2C receptors is the principal mechanism underlying its DS properties.

Topics: 8-Hydroxy-2-(di-n-propylamino)tetralin; Aminopyridines; Animals; Conditioning, Operant; Ethylamines; Fluorobenzenes; Indoles; Male; Mianserin; Piperazines; Piperidines; Pyrazines; Rats; Rats, Wistar; Receptor, Serotonin, 5-HT2C; Receptors, Serotonin; Reinforcement, Psychology; Serotonin Antagonists; Serotonin Receptor Agonists; Thiophenes

The mixed 5-HT2A/5-HT2B/5-HT2C receptor agonist, m-(chlorophenyl)piperazine (mCPP), elicited penile erections in rats, an action mimicked by the selective 5-HT2C receptor agonist, RO 60-0175 (S)-2-(6-chloro-5-fluoroindol-1-yl)-1-methylethylamine), whereas the preferential 5-HT2B receptor agonist, BW 723C86 (1-[5-(thienylmethoxy)-1H-3-indoyl] propan-2-amine) was ineffective. The actions of mCPP and RO 60-0175 were dose-dependently abolished by the novel 5-HT2B/5-HT2C receptor antagonists, SB 200,646 (1-(1-methylindol-5-yl)-3-(3-pyridyl) urea) and SB 206,553 (5 methyl-1-(3-pyridil-carbamoyl)-1,2,3,5-tetrahydropyrrolo[2,3 -f]indole). In contrast, penile erections were not significantly affected by the selective 5-HT2B receptor antagonist, SB 204,741 (1-(1-methylindol-5-yl)-3-(3-methylisothiazol-5-yl)-urea) nor by the selective 5-HT2A receptor antagonist, MDL 100,907 ([R(+)-alpha-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenylethyl)]-4-p iperidine-methanol]). These data provide rigorous pharmacological evidence that activation of 5-HT2C receptor elicits penile erections in the rat. This model should, thus, be of use for characterising novel ligands at this site.

Topics: Animals; Dose-Response Relationship, Drug; Ethylamines; Indoles; Male; Penile Erection; Piperazines; Pyridines; Rats; Rats, Wistar; Receptor, Serotonin, 5-HT2C; Receptors, Serotonin; Serotonin Antagonists; Serotonin Receptor Agonists; Thiophenes; Urea