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PubMed1993

The effects of ritanserin on mood and sleep in abstinent alcoholic patients.

A trial was carried out to determine the effect of ritanserin or a placebo on sleep and mood in two groups of abstinent alcoholic patients. Their condition was characterized by both alcohol dependence and dysthymia, associated with a personality disorder. They were included in the study after 30 days of sobriety. Ritanserin was given at a daily dose of 10 mg for 28 days and was preceded (10 days) and followed (2 days) by a placebo. Plasma ritanserin concentration after administration of the 28th dose was higher than after the first dose. Peak levels of ritanserin from the first to the 28th dose increased approximately three-fold. In the ritanserin group there was a reduction of total waking time. Total sleep time increase was associated with significantly larger amounts of nonrapid eye movement sleep. Slow wave sleep and rapid eye movement sleep (in minutes or as a percent of total sleep time) were not significantly modified. Patients on ritanserin achieved a progressive improvement of their dysthymia. As compared to the placebo group, a statistically significant decrease of the Hamilton Rating Scale for Depression and Hamilton Rating Scale for Anxiety was found in the ritanserin group after 1 week of treatment. The absence of an effect in the placebo-treated group suggests that the clinical response and sleep improvement were mainly related to ritanserin administration.

Adult↗
PubMed1993

Effects of ritanserin, a selective and specific S2-serotonergic antagonist, on portal pressure and splanchnic hemodynamics in rats with long-term bile duct ligation.

This study investigated the short-term effects of ritanserin, a selective and specific S2-serotonergic antagonist, in an experimental model of cirrhosis and intrahepatic portal hypertension caused by long-term bile duct ligation and division and in normal control rats. The rats subjected to bile duct ligation were randomized under blind conditions into two groups to receive ritanserin (0.7 mg/kg body wt, intravenously; n = 10) or the same volume of placebo (isotonic saline solution; n = 10). We performed hemodynamic studies with radiolabeled microspheres 60 min after drug administration. Two groups of normal rats (n = 6) were studied after they received ritanserin or placebo. Ritanserin administration to rats subjected to bile duct ligation significantly reduced portal pressure (from 16.2 +/- 1.3 mm Hg to 12.3 +/- 0.7 mm Hg; mean decrease, 22% +/- 5%; p < 0.05). This reduction was associated with lower portal venous resistance (4.3 +/- 0.5 mm Hg.min.100gm/ml in the placebo group vs. 3.1 +/- 0.3 mm Hg.min.100 gm/ml in rats given ritanserin; mean decrease, 28%; p = 0.069), but we saw no changes in portal vein inflow (3.9 +/- 0.5 ml/min.100 gm vs. 4.4 +/- 0.4 ml/min.100 gm), mean arterial pressure (110 +/- 9 mm Hg vs. 102 +/- 9 mm Hg) and cardiac index (32.9 +/- 2.7 ml/min.100 gm vs. 40.5 +/- 6.7 ml/min.100 gm). Hepatic arterial and kidney blood flows were not modified by ritanserin. Ritanserin had no systemic or splanchnic effects in normal rats. Our results demonstrate that ritanserin infusion decreases portal pressure without any systemic hemodynamic change in rats with secondary biliary cirrhosis and portal hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Failure of ritanserin to block the discriminative or reinforcing stimulus effects of cocaine.

Ritanserin, a 5-HT2/1C antagonist, has been suggested to reduce the preference for cocaine in rats. In the present experiment, the action of ritanserin was investigated in locomotor activity, cocaine drug discrimination, and cocaine self-administration paradigms in rats. A low dose of ritanserin (1.0 mg/kg) was without effect on locomotor activity, while a higher dose (10.0 mg/kg) reduced both horizontal and vertical locomotor activity counts during the first 30 min of the test session. Ritanserin (0.32-32 mg/kg) did not significantly affect the discrimination of 10 mg/kg of cocaine, nor did a dose of 10.0 mg/kg significantly modify the dose-effect curve for cocaine discrimination. Ritanserin (1.0 and 10.0 mg/kg) had no significant effect on the dose-response curve for cocaine self-administration. Thus, ritanserin was without effect against either the discriminative or reinforcing stimulus effects of cocaine, suggesting that ritanserin has limited efficacy as a potential treatment for cocaine abuse.

Animals↗
PubMed1990

Effects of zimeldine, a selective 5-HT reuptake inhibitor, combined with ritanserin, a selective 5-HT2 antagonist, on waking and sleep stages in rats.

Sleep and waking in rats were studied 8 h following administration of a selective 5-hydroxytryptamine (5-HT) reuptake inhibitor (zimeldine), a selective 5-HT2 antagonist (ritanserin) and a combination of ritanserin and zimeldine. Consistent with earlier findings, zimeldine gave a biphasic effect on sleep and waking. Waking was increased the first 3 h, followed by an increase in deep slow wave sleep (SWS-2), maximal in hours 4 and 5. Ritanserin gave an increase in SWS-2 that was spread out over the recording period. Ritanserin + zimeldine also gave a biphasic effect as zimeldine did, and the initial increase in waking and the following increase in SWS-2 tended to be stronger. Thus, ritanserin did not block the initial waking effect seen after zimeldine administration, indicating that this waking effect was not due to 5-HT2 stimulation. The increase in SWS-2 seemed to reflect an addition of the increases following the zimeldine and ritanserin alone conditions. This suggests that the increase in SWS-2 seen after 5-HT reuptake inhibition and 5-HT2 blockade are independent phenomena. Zimeldine alone, ritanserin alone and the combination all gave a clear reduction of rapid eye movement sleep.

Animals↗
PubMed2005

Microinjection of ritanserin into the CA1 region of hippocampus improves scopolamine-induced amnesia in adult male rats.

The effect of ritanserin (5-HT2 antagonist) on scopolamine (muscarinic cholinergic antagonist)-induced amnesia in Morris water maze (MWM) was investigated. Rats were divided into eight groups and bilaterally cannulated into CA1 region of the hippocampus. One week later, they received repeatedly vehicles (saline, DMSO, saline+DMSO), scopolamine (2 microg/0.5 microl saline/side; 30 min before training), ritanserin (2, 4 and 8 microg/0.5 microl DMSO/side; 20 min before training) and scopolamine (2 microg/0.5 microl; 30 min before ritanserin injection)+ritanserin (4 microg/0.5 microl DMSO) through cannulae each day. Animals were tested for four consecutive days (4 trial/day) in MWM during which the position of hidden platform was unchanged. In the fifth day, the platform was elevated above the water surface in another position to evaluate the function of motor, motivational and visual systems. The results showed a significant increase in escape latencies and traveled distances to find platform in scopolamine-treated group as compared to saline group. Ritanserin-treated rats (4 microg/0.5 microl/side) showed a significant decrease in the mentioned parameters as compared to DMSO-treated group. However, scopolamine and ritanserin co-administration resulted in a significant decrease in escape latencies and traveled distances as compared to the scopolamine-treated rats. Our findings show that microinjection of ritanserin into the CA1 region of the hippocampus improves the scopolamine-induced amnesia.

Amnesia↗
PubMed1987

Does acute serotonergic type-2 antagonism reduce blood pressure? Comparative effects of single doses of ritanserin and ketanserin in essential hypertension.

We have studied the acute effects of the serotonergic type-2 (5-HT2) antagonists ketanserin and ritanserin given as single oral doses to patients with essential hypertension. Ketanserin has alpha 1-antagonist properties, whereas ritanserin is largely devoid of alpha 1-receptor binding affinity. Ketanserin (40 mg orally) caused a significant reduction (p less than 0.03) of sitting mean arterial pressure over the 8-h period following drug administration by an average of 15.4 +/- 3.2 mm Hg (mean +/- SEM) as compared to a reduction of 8.5 +/- 2.2 following placebo. In contrast, ritanserin had no significant effect on blood pressure compared to placebo; sitting mean arterial pressure was reduced by 9.0 +/- 2.6 and 10.8 +/- 1.8 mm Hg after administration of 10 and 20 mg, respectively, of ritanserin. There were no significant differences in pulse rate among placebo, ketanserin, or ritanserin phases. Ritanserin caused a reduction in the hostility score (p less than 0.05) as measured by the Multiple Affect Adjective Check List; ketanserin had no significant effects. The highly selective 5-HT2 antagonist ritanserin, given in a dose which caused measurable alteration of psychological function tests, had no acute effects on blood pressure. The acute antihypertensive effects of ketanserin are not caused by 5-HT2 antagonism alone, but are likely to be dependent on its alpha 1-antagonistic properties.

Adult↗
PubMed1997

Power spectral electroencephalogram analysis of the effects of ritanserin in freely moving rats during quiet waking.

Changes in the spectral characteristics of the Fast Fourier Transformed (FFT) electroencephalogram (EEG) recorded from the frontal cortex of freely moving rats during quiet waking were studied after blockade of the 5-hydroxytryptamine-2 (5-HT2) receptors by the potent and long acting 5-HT2 antagonist ritanserin administered intraperitoneally (i.p.) at two doses (0.63 and 2.5 mg/kg). The rationale of this approach was to evaluate the subtle ritanserin-induced changes in the EEG in the frequency domain, and thus obtain more information about the neurophysiological effects mediated by brain 5-HT2 receptors and about the mechanisms underlying ritanserin's ability to increase sleep at the expense of wakefulness. Ritanserin induced significant changes in the power spectrum of EEG recorded from the frontal cortex. The activation index (the ratio of the dominant frequency in the power spectrum to the total power) significantly decreased after ritanserin, which was due to the increased EEG power in all frequency bands (except for beta 2) and to the decreased dominant frequency in the EEG spectrum, suggesting ritanserin-reduced EEG activation during quiet waking. The results favor the view of the excitatory modulating action of serotonin mediated via cortical 5-HT2 receptors and suggest that ritanserin could cause a faster transition from waking to sleep.

Animals↗
PubMed1991

Pharmacokinetics of ritanserin in patients undergoing hemodialysis.

The pharmacokinetics of ritanserin were studied in five patients with chronic renal insufficiency and who were undergoing periodic hemodialysis. Immediately after breakfast, a single 10-mg ritanserin tablet was administered to each patient on a day that they did not undergo dialysis. Plasma ritanserin levels were measured by a specific high-performance liquid chromatographic assay sensitive to 2 ng/mL plasma. After the oral 10-mg dose, the average time to reach the peak plasma concentration, Tmax, was 4.4 +/- 2.2 hours in these uremic patients, with a range of 2 to 8 hours. The average peak plasma concentration was 73.6 +/- 26.9 ng/mL (range: 54.6-120.0 ng/mL). Compared with a previous study in healthy volunteers, the uremic patients had a slower absorption profile, with a 39% reduction in peak plasma concentration and mean delay of 2.5 hours in Tmax. The mean area under the plasma concentration-time curve for ritanserin (2031 +/- 636 ng.hr/mL) was 47% lower compared with that in healthy volunteers (3867 +/- 1413 ng.hr/mL). The observed delayed and lower ritanserin absorption in these uremic patients may be caused by the chronic use of antacids such as aluminum hydroxide and calcium carbonate in all patients and/or by concurrent pathologic changes in the gastrointestinal mucosa of these patients. The regular hemodialysis sessions every 2-3 days did not affect the elimination rate of ritanserin, as the terminal half-life in these patients (39 +/- 23 hr) is similar to that in healthy volunteers (41 +/- 14 hr).

Administration, Oral↗
PubMed1987

Allosteric properties of the 5-HT2 receptor system of the rat tail artery. Ritanserin and methysergide are not competitive 5-HT2 receptor antagonists but allosteric modulators.

We present an analysis of the interactions of 5-hydroxytryptamine (5-HT) and antagonists (methysergide, ketanserin, ritanserin) with the 5-HT2 receptor system of strips of rat tail artery. The mode of action of ritanserin was also studied on strips of calf coronary arteries. 1. Ketanserin competitively antagonized 5-HT-induced effects in rat tail artery with an affinity (pKB = 9.4 nmol/l) consistent with the assumption of an interaction of 5-HT and ketanserin at 5-HT2-receptors. 2. Methysergide reduced to 50-60% the maximum response to 5-HT in rat tail artery. Concentration-effect curves for 5-HT became biphasic in the presence of methysergide with quickly and slowly developing contractions at low and high concentrations of 5-HT, respectively. 100 nmol/l ketanserin completely restored effects of 5-HT depressed by low concentrations of methysergide (less than 10 nmol/l). Higher concentrations of methysergide in the presence of 100 nmol/l ketanserin again depressed the effects of 5-HT. 3. Ritanserin resembles methysergide by causing insurmountable antagonism of 5-HT-induced contractions which can be prevented by ketanserin in both rat tail artery and calf coronary artery. These results are inconsistent with competition between ritanserin and 5-HT for the 5-HT2 receptor. 4. The findings are consistent with the assumption of an interaction of ketanserin and methysergide or ritanserin with an allosteric site near the 5-HT2-receptor. Both methysergide and ritanserin appear to antagonize the effects of 5-HT through an allosteric site which is distinct from the 5-HT2 receptor.

Allosteric Regulation↗
PubMed1996

Effects of the 5-HT2 receptor antagonist ritanserin on halothane-induced increase of inositol phosphates in porcine malignant hyperthermia.

Recent studies have shown a significant increase of inositol phosphates (IPs) in skeletal muscle during episodes of halothane-induced malignant hyperthermia (MH) in pigs. After treatment with dantrolene and disappearance of MH crisis the IP concentrations returned to basal levels. In order to examine if the increase of IPs during halothane-induced MH may be related to an enhanced IP synthesis in response to activation of 5-HT2 (5-hydroxytryptamine) receptors, the effects of ritanserin, a selective 5-HT2 receptor antagonist, on IP levels were investigated. Biopsies of skeletal muscle of the hindlimbs were obtained in random order and IPs were determined in homozygous MH-susceptible (MHS) and MH-non-susceptible (MHN) swine in the following order: (1) basal, (2) after treatment with ritanserin (2.0 mg/kg), (3) after halothane challenge (3 vol% for 20 min). Basal concentrations of all IPs were higher in MHS than in MHN swine. Ritanserin did not cause any significant changes of IP levels compared to the basal concentrations in MHS and MHN pigs. In MHS pigs, ritanserin did not prevent a halothane-induced MH-crisis. After halothane challenge, 1,3,4-IP3, 1,3,4,6-IP4 and 1,3,4,5-IP4 levels were increased in MHS (during MH crisis) vs. basal concentrations, whereas no changes were found in MHN pigs. Since the increases of IP levels in MHS pigs during MH crisis found in the present study were comparable to those without pretreatment with ritanserin, shown by recent studies, it may be concluded that ritanserin does not prevent the increase of IPs during a halothane-induced MH. Thus, the present data indicate that increases of IP levels during halothane-induced MH in swine are due to other mechanisms than 5-HT mediated enhancement of IP synthesis.

Anesthetics, Inhalation↗
PubMed1986

Down regulation of serotonin-S2 receptor sites in rat brain by chronic treatment with the serotonin-S2 antagonists: ritanserin and setoperone.

Ritanserin is a potent and selective serotonin-S2 antagonist which slowly dissociates from the receptor sites, while setoperone has potent serotonin and moderate dopamine antagonistic properties and dissociates rapidly from the receptor sites. Acute administration of ritanserin (1-10 mg/kg) produced a non-competitive inhibition of 3H-ketanserin binding, measured ex vivo in washed frontal cortex membranes, which lasted for 12 h. This is in accordance with the slow dissociation of the drug from the receptor sites. Setoperone (1-10 mg/kg orally) also produced a partially non-competitive inhibition of 3H-ketanserin binding in washed membranes, which is unlike its rapid dissociation. In contrast, there was no inhibition of dopamine receptor binding in washed striatal membranes. Chronic oral administration of 10 mg/kg X day of the drugs significantly reduced the Bmax values of 3H-ketanserin, without changing the KD value when drug-free periods were longer than 1 day. The maximum reduction following 25 days' treatment with 14 mg/kg ritanserin was 50% at 1 day drug-free; the Bmax values gradually returned to the control value in about 12 days. The receptor half-life was calculated to be 3.5 days and the receptor synthesis rate 4 fmoles/mg tissue X day. Ritanserin treatment did not alter radioligand binding to serotonin-S1, alpha 1-, alpha 2- and beta-adrenergic, dopamine-D2, benzodiazepine and substance P sites. Chronic treatment with setoperone at 10 mg/kg X day, orally, significantly reduced the Bmax value of 3H-ketanserin binding in frontal cortex but treatment with 1 mg/kg X day did not. In contrast, a dose-dependent increase in the number of striatal dopamine-D2 sites was observed, in accordance with the moderate dopamine-antagonistic properties of setoperone. Dopamine-D2 receptor up regulation up to 150% of control values, was maintained at the same level for 9 days, it started to decline 12 days after stopping drug treatment. Following chronic treatment and drug withdrawal for more than 1 day, ritanserin and setoperone levels in whole brain homogenates were below detection level (less than 1 ng/g). The similar reduction in the Bmax values of 3H-ketanserin binding following chronic treatment with the rapidly dissociating setoperone and the slowly dissociating ritanserin, the absence of effect on the KD value, the slow reappearance of the receptor sites and the opposite effect on serotonin-S2 and dopamine-D2 receptors with setoperone suggest that real serotonin-S2 receptor down regulation occurs following antagonist treatment. The findings illustrate the difference in receptor regulation between the serotonergic and the dopaminergic system.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1988

Effects of ritanserin on sleep disturbances of dysthymic patients.

Ritanserin, a selective and potent serotonin-2 antagonist, is effective in the treatment of a variety of syndromes related to anxiety and depression, including dysthymic disorder. In animals and healthy volunteers, ritanserin specifically increases slow-wave sleep and the hypothesis arises that this effect on sleep may contribute to its therapeutic properties. Therefore, we studied the effects of ritanserin on sleep in a group of dysthymic patients (DSM-III). Polygraphic recording as well as subjective evaluations of the quality of sleep were performed before and at the end of a 4-week period of double-blind medication with either ritanserin (10 mg o.d. in the morning) or placebo. At baseline, patients showed at fragmented and superficial sleep, with low amounts of slow wave sleep. Ritanserin significantly increased Slow Wave Sleep and changed the frequency and distribution of some stage transitions during the night. No other sleep parameters were modified by ritanserin treatment.

Adult↗
PubMed1998

A randomised double-blind 16-week study of ritanserin in fibromyalgia syndrome: clinical outcome and analysis of autoantibodies to serotonin, gangliosides and phospholipids.

The aim of the study was to evaluate in a double-blind manner the effect of the long-acting 5-hydroxytryptamine 2 (5-HT2)-receptor blocker Ritanserin on clinical symptoms in patients with fibromyalgia syndrome (FM) and on production of antibodies to serotonin, gangliosides and phospholipids, recently shown to have a high incidence in this disease. Fifty-one female patients with typical FM were included in the 16-week study: 24 received Ritanserin and 27 received a placebo. Antibodies to 5-HT, gangliosides (Gm1) and phospholipids (thromboplastin) were determined by enzyme-linked immunosorbent assay at day 0 and at the end of week 16. The psychological and physical status, including tender points, of the patients was evaluated at day 0 and at the end of weeks 4 and 16. At the end of the study, there was an improvement (p < 0.05) in feeling refreshed in the morning in the Ritanserin-treated group and headache was also significantly improved compared with the placebo group. There was no difference in pain, fatigue, sleep, morning stiffness, anxiety and tender point counts in the Ritanserin and placebo groups. Fifty-one per cent of the 51 patients had at least one of the three antibodies to 5-HT, Gm1 and phospholipids. The incidence and activity of these antibodies were not influenced by Ritanserin or placebo. The observation that Ritanserin has only a small effect on clinical symptoms indicates that disturbances in serotonin metabolism or uptake may be only one factor in the pathogenesis of the disease. The high incidence of a defined autoantibody pattern in FM could again be confirmed in this study. However, it remains speculative whether immunological reactions are, indeed, involved.

Adult↗
PubMed1990

The serotonin2 antagonist ritanserin blocks quasi-morphine withdrawal at a time when mianserin is no longer effective.

A quasi-morphine withdrawal syndrome (QMWS), produced in opiate-naive rats with an injection of isobutylmethylxanthine (IBMX) and the opioid antagonist naloxone, allows one to study the expression of opiate withdrawal in the absence of the acute or chronic effects of opiates and the adaptive processes termed dependence. The allegedly selective and long-acting serotonin2 (5-HT2) antagonist ritanserin attenuated the QMWS-induced suppression of fixed ratio (FR) operant responding, which is a sensitive measure of the expression of a QMWS. When administered 30 min prior to precipitation of the QMWS, the lowest dose of ritanserin tested (0.158 mg/kg) was the most effective in blocking the expression of withdrawal; however, there was not complete reversal of the behavioral suppression. Acutely, the two higher doses of ritanserin tested (2.5 and 10 mg/kg) suppressed responding when given alone. This may have masked their ability to attenuate a QMWS. At a dose of 2.5 mg/kg, ritanserin completely blocked the QMWS-induced suppression of responding 24 h post-administration, at a time when its actions at other receptors (e.g., alpha 2) have dissipated. At an equivalent dose, the shorter-acting 5-HT2 antagonist mianserin was unable to attenuate the QMWS-induced suppression of FR operant responding 24 h post-administration. The 5-HT2 antagonists reportedly produce a paradoxical down-regulation of 5-HT2 binding sites upon chronic treatment, rather than the expected supersensitivity. Chronic treatment with ritanserin (2.5 mg/kg/day for 7 days), but not mianserin (same regimen), attenuated a QMWS 24 h after the final injection, thus supporting with a functional measure, the down-regulation of such binding sites by ritanserin.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-3-isobutylxanthine↗
PubMed2001

Subchronic effects of the GABA-agonist lorazepam and the 5-HT2A/2C antagonist ritanserin on driving performance, slow wave sleep and daytime sleepiness in healthy volunteers.

RATIONALE: Lorazepam, a benzodiazepine anxiolytic, may increase daytime sleepiness and impair psychomotor performance, which is hazardous for patients engaging in daily activities such as car driving. Given current prescription practice, information on the repeated dose effects is required. The 5-HT2A/2C antagonist ritanserin was originally developed as a safer alternative to the benzodiazepines, yet having limited clinical efficacy. 5HT2A/2C receptors have been implicated in regulating slow-wave sleep but little is known about their role in human performance. OBJECTIVE: The present study investigated the subchronic effects of the benzodiazepine anxiolytic lorazepam and the 5-HT2A/2C antagonist ritanserin on actual driving performance, objective and subjective sleepiness, and nocturnal slow wave sleep. METHODS: Eighteen healthy volunteers were treated twice daily for 7 days with ritanserin 5 mg, lorazepam 1.5 mg or placebo. Treatments were administered according to a double-blind, cross-over design. Tests were performed on day 7 of each treatment week. Sleep EEG was recorded during the preceding night. RESULTS: Lorazepam had a pronounced impairing effect on lateral position control and induced daytime sleepiness, while having no effect on other parameters. In contrast, ritanserin did not impair driving performance or affect objectively measured daytime sleepiness, while subjects reported to feel more alert during daytime. Moreover, consistent with its effects on 5-HT2 receptors, ritanserin increased the amount of nocturnal slow wave sleep. There were no relationships between changes in slow wave sleep and performance parameters. CONCLUSIONS: Lorazepam administered for 7 consecutive days may be hazardous for patients who engage in driving activities. Antagonism of 5-HT2A/2C receptors, as accomplished by ritanserin, increases slow wave sleep and is devoid of effects on objective sleepiness and driving behaviour. Whether this extends to other cognitive and psychomotor domains remains to be established.

Adult↗
PubMed1990

Ritanserin decreases portal pressure in conscious and unrestrained cirrhotic rats.

We have recently demonstrated that ritanserin, a serotonin 5-hydroxytryptamine receptor antagonist void of systemic effects, caused a significant reduction of portal pressure in conscious cirrhotic dogs. The mechanism by which ritanserin lowers portal pressure is poorly defined. We investigated the splanchnic and systemic hemodynamic effects of ritanserin (0.63 mg/kg body wt i.v., a dose known to completely inhibit binding of 5-hydroxytryptamine to its receptors), in conscious and unrestrained cirrhotic rats (n = 13). Heparinized catheters were placed into the portal vein, inferior vena cava, aorta, and left ventricle with exit from the neck. Hemodynamic studies were performed 4 h after consciousness was regained. Cardiac output and regional blood flows were measured using radiolabeled microspheres and the reference sample method. Sixty minutes after administration, ritanserin caused a significant reduction of portal pressure (-17%) with minimal changes in portal venous inflow (+3%). Portal vascular resistance decreased significantly (-23%), whereas splanchnic arteriolar resistance was similar before and after ritanserin. A significant increase in mean arterial pressure (+5%) and cardiac output (+22%) was observed. Our results suggest that ritanserin lowers portal pressure through a mechanism separate from portal venous inflow. This effect could be due to changes in intrahepatic or on portocollateral resistances, or both. These findings support the potential use of this new agent in the treatment of portal hypertension.

Animals↗
PubMed1993

Effects of acute and subchronic administration of ritanserin on the social behaviour of mice.

The effects of ritanserin on the behaviour of adult male CD1 mice were examined after acute intraperitoneal injection (0.1, 0.3 and 0.6 mg/kg) and after administration for 12-15 days in the drinking fluid at 1.6 mg/l (0.32 mg/kg daily) and 3.1 mg/l (0.7 mg/kg daily). The behaviour of each mouse was examined by ethological procedures during 5 min social encounters with an untreated partner in an aversive situation, an unfamiliar neutral cage, and in a familiar situation, the animal's home cage. Behaviour also was monitored for 5 min in the light-dark box. In the acute studies, behavioural observations commenced at 30 min after injection. In the home cage, ritanserin significantly increased social investigation during social encounters and reduced exploratory activity at all doses tested, after both acute and subchronic administration. In the neutral cage, acutely administered ritanserin increased social investigation and reduced non-social activity at all dose levels. Effects were maximal at 0.3 mg/kg, and at this dose it also increased aggression. In the neutral cage after subchronic administration, ritanserin at both dose levels increased aggression, digging and investigation of the substrate and occurrence of the social act, "attend", while reducing the time spent in non-social exploration. Ritanserin did not affect behaviour in the light-dark box. The significance of these findings relative to the anxiolytic and antidepressant effects of ritanserin is discussed.

Administration, Oral↗
PubMed1989

Antinociceptive effects of the 5-HT2 antagonist ritanserin in rats: evidence for an activation of descending monoaminergic pathways in the spinal cord.

The antinociceptive properties of the 5-HT2 antagonist ritanserin have been investigated in the writhing test using rats implanted with chronic lumbar catheters. The antinociceptive action of 15 mg/kg ritanserin applied subcutaneously (s.c.) was powerfully inhibited by the intrathecal (i.t.) application of ritanserin (50 nmol), methysergide (15 nmol), yohimbine (20 nmol), alpha-flupenthixol (20 nmol) or naloxone (15 nmol), but not atropine (30 nmol), at doses which themselves produced no change in nociceptive threshold. It is concluded that ritanserin acts supraspinally to activate pain-modulating descending serotonergic, noradrenergic, dopaminergic and possibly opioidergic pathways, while spinopetal cholinergic pathways do not seem to be involved. Hyperalgesic effects of s.c. ritanserin following the i.t. application of methysergide or yohimbine were interpreted in terms of the co-release of an excitatory transmitter, possibly substance P, from descending serotonergic and noradrenergic nerve fibres. The supraspinal mechanism by which ritanserin activates spinopetal pathways and its dependence on 5-HT2 receptors have not yet been established.

Animals↗