Effects Of Mianserin Research Articles

The Effect of Mianserin on Lifespan of Caenorhabditis elegan is Abolished by Glucose.

The antidepressant Mianserin has been shown to extend the lifespan of Caenorhabditis elegan (C. elegan), a well-established model organism used in ageing research. The extension of lifespan in C. elegan was shown to be dependent on increased expression of the scaffolding protein (ANK3/unc-44). In contrast, antidepressant use in humans is associated with an increased risk of death. The C. elegan elegan in the laboratory are fed Escherichia coli (E. coli), a diet high in protein and low in carbohydrate, whereas a typical human diet is high in carbohydrates. We hypothesized that dietary carbohydrates might mitigate the lifespan-extension effect of mianserin. To investigate the effect of glucose added to the diet of C. elegan on the lifespan-extension effect of mianserin. Wild-type Bristol N2 and ANK3/unc-44 inactivating mutants were cultured on agar plates containing nematode growth medium and fed E. coli. Treatment groups included (C) control, (M50) 50 μM mianserin, (G) 73 mM glucose, and (M50G) 50 μM mianserin and 73 mM glucose. Lifespan was determined by monitoring the worms until they died. Statistical analysis was performed using the Kaplan-Meier version of the log-rank test. Mianserin treatment resulted in a 12% increase in lifespan (P<0.05) of wild-type Bristol N2 worms but reduced lifespan by 6% in ANK3/unc-44 mutants, consistent with previous research. The addition of glucose to the diet reduced the lifespan of both strains of worms and abolished the lifespan-extension by mianserin. The addition of glucose to the diet of C. elegan abolishes the lifespan-extension effects of mianserin.

The atypical antidepressant mianserin exhibits agonist activity at κ‐opioid receptors

Antidepressants are known to interact with the opioid system through mechanisms not completely understood. We previously reported that tricyclic antidepressants act as agonists at distinct opioid receptors. Here, we investigated the effect of the atypical antidepressant mianserin at cloned and native opioid receptors. Effects of mianserin were examined in CHO cells transfected with human opioid receptors, C6 glioma cells and rat brain membranes by the use of radioligand binding and functional assays including the stimulation of [(35)S]GTPγS binding and MAPK phosphorylation. Mianserin displayed 12- and 18-fold higher affinity for κ- than µ- and δ-opioid receptors respectively. In [(35)S]GTPγS assays, mianserin selectively activated κ-opioid receptors. The agonist activity was antagonized by the selective κ-opioid blocker nor-binaltorphimine (nor-BNI). The mianserin analogue mirtazapine also displayed κ-opioid agonist activity. Mianserin and mirtazapine increased ERK1/2 phosphorylation in CHO cells expressing κ-opioid receptors and C6 cells, and these effects were antagonized by nor-BNI. In rat striatum and nucleus accumbens, mianserin stimulated [35S]GTPγS binding in a nor-BNI-sensitive manner with maximal effects lower than those of the full κ-opioid agonists (-)-U50,488 and dynorphin A. When combined, mianserin antagonized the effects of the full κ-opioid receptor agonists in [(35)S]GTPγS assays and reduced the stimulation of p38 MAPK and ERK1/2 phosphorylation by dynorphin A. In different cell systems, mianserin directly activates κ-opioid receptors, displaying partial agonist activity at brain receptors. Thus, this property appears to be a common feature of different classes of antidepressants.

Postjunctional effects of mianserin and its metabolites on the rat isolated anococcygeus muscle.

After rat isolated anococcygeus muscle had been treated with 6-hydroxydopamine to abolish noradrenergic transmission, the effects of mianserin and its metabolites alone on tone and on the contractile responses to methacholine and phenylephrine were studied. Mianserin (greater than or equal to 3 X 10(-5) M) and 8-hydroxymianserin (greater than or equal to 3 X 10(-6) M), but not desmethylmianserin and mianserin-N-oxide, induced contractions. The contractions to mianserin were not altered by phentolamine, atropine, cyproheptadine, ouabain and verapamil but were reduced in tissues treated with indomethacin. Thus the responses to mianserin may, in part, be mediated by the synthesis of prostaglandins. Mianserin (10(-5) M) and 8-hydroxymianserin (10(-7)-10(-5) M) potentiated, mianserin-N-oxide had no effect, and desmethylmianserin (10(-7)-10(-5) M) inhibited methacholine-induced contractions. The inhibition of responses to phenylephrine was concentration-related with desmethylmianserin (10(-7)-10(-5) M) and mianserin-N-oxide (10(-6)-10(-5) M) but not with mianserin or 8-hydroxymianserin (10(-7)-10(-5) M). The effects of mianserin and its metabolites on responses to methacholine and phenylephrine were similar in the absence and presence of indomethacin. These results suggest that mianserin and 8-hydroxymianserin increase the tissue's sensitivity to methacholine by an action at the level, or distal to, the muscarine receptor. In addition to blocking alpha 1-adrenoceptors, mianserin and 8-hydroxymianserin may have another postjunctional action at, or beyond, the alpha 1-adrenoceptor.

The Effect of Mianserin and Trazodone on Body Weight and Serum Tryptophan in Dietary-Obese Rats

The Effect of Mianserin and Trazodone on Body Weight and Serum Tryptophan in Dietary-Obese Rats S A Pleece, S A Pleece Pharmacology Group, School of Pharmacy and Pharmacology, University of Bath, Claverton Down, Bath, BA2 7AY Search for other works by this author on: Oxford Academic Google Scholar M J Kirby, M J Kirby Pharmacology Group, School of Pharmacy and Pharmacology, University of Bath, Claverton Down, Bath, BA2 7AY Search for other works by this author on: Oxford Academic Google Scholar P H Redfern P H Redfern Pharmacology Group, School of Pharmacy and Pharmacology, University of Bath, Claverton Down, Bath, BA2 7AY Search for other works by this author on: Oxford Academic Google Scholar Journal of Pharmacy and Pharmacology, Volume 34, Issue Supplement_12, December 1982, Page 103P, https://doi.org/10.1111/j.2042-7158.1982.tb00934.x Published: 12 April 2011

Influence of changes in protein binding on the central activity of antidepressants.

The central effect (expressed as analgesic response), protein binding and brain uptake of mianserin were measured in mice receiving drug intraperitoneally. A significant decrease of the central effect of mianserin (30 mg kg-1) was seen in mice with experimental inflammation when compared with control animals (reaction time (s) = 12.12 +/- 1.22 vs 25.56 +/- 2.92; P less than 0.001) and the dose-analgesia response curve (10-60 mg kg-1) was significantly shifted to the right in mice with inflammation. In serum of mice with inflammation, unbound concentration of mianserin was decreased from 19.37 +/- 0.73 to 17.83 +/- 0.30% (P less than 0.05) and seromucoid levels were significantly increased (P less than 0.001). Following the intraperitoneal administration of 30 mg kg-1 of mianserin, brain uptake decreased in diseased mice when compared with control animals (P less than 0.02), suggesting that the decrease in analgesia was secondary to a decrease in drug delivery to the brain because of increased protein binding.

Role of Endogenous Serotonin in Modulating Genioglossus Muscle Activity in Awake and Sleeping Rats

Exogenous serotonin at the hypoglossal motor nucleus (HMN) stimulates genioglossus (GG) muscle activity. However, whether endogenous serotonin contributes to GG activation across natural sleep-wake states has not been determined, but is relevant given that serotonergic neurons have decreased activity in sleep and project to pharyngeal motoneurons. To determine the role of endogenous serotonin at the HMN in modulating GG activity across natural sleep-wake states. Ten rats were implanted with electroencephalogram and neck muscle electrodes to record sleep-wake states, and GG and diaphragm wires for respiratory muscle recordings. Microdialysis probes were implanted into the HMN for perfusion of artificial cerebrospinal fluid and the serotonin receptor antagonist mianserin (100 microM). In room air, there was no effect of mianserin on respiratory-related or tonic GG activities across sleep-wake states (p > 0.300). In hypercapnia, however, the normal declines in GG activity from non-REM to REM sleep, and wakefulness to REM sleep, were reduced with mianserin (p < 0.005). These data demonstrate a normally low endogenous serotonergic drive modulating GG activity unless augmented by reflex inputs. We also demonstrated a significant serotonergic drive modulating GG activity in vagotomized rats, but not in vagi-intact rats, under anesthesia, suggesting that previous results in reduced preparations may have been influenced by vagotomy. The results show a minimal endogenous serotonergic drive at the HMN modulating GG activity across sleep-wake states, unless augmented by reflex inputs. This result has implications for pharmacologic strategies aiming to increase GG activity by manipulating endogenous serotonin in patients with obstructive sleep apnea.

Interaction between the tetracyclic antidepressant mianserin HCl and opioid receptors

The antinociceptive effects of the tetracyclic antidepressant mianserin and its interaction with various opioid receptor subtypes was evaluated. Mice were tested with a hotplate analgesia meter. Mianserin elicited an antinociceptive effect in a dose–dependent manner following doses from 1–25 mg/kg. As the mianserin dose increased beyond 30 mg/kg, latencies returned to baseline, yielding a biphasic effect. This effect of mianserin was antagonized by naloxone ( P<0.005), implying a possible opioid mechanism of action involved in the mianserin induced antinociceptive effect. When administered with various opioid antagonists, the sensitivity of mianserin to selective opioid antagonists was found significant for μ and κ1 opioid receptor subtypes ( P<0.005), but not for δ-receptor. At the next stage mianserin was administered together with various agonists of opioid receptors. When administered together with opiates, mianserin significantly potentiates analgesia at the μ, κ1 and κ3 opioid receptor subtype ( P<0.005) and to a lesser extent, at the δ opioid receptors. These results suggest a potential use of mianserin in the management of some pain syndromes. However, further research is needed in order to establish both the exact clinical indications and the effective doses of mianserin when prescribed for pain.

ミアンセリンの身体状態に対する影響

ミアンセリンの身体状態に対する影響

Effects of mianserin and ketanserin on lordosis behavior after systemic treatment or infusion into the ventromedial nucleus of the hypothalamus

The effects of the 5-HT 2A/2C antagonists, mianserin and ketanserin, were investigated in proestrous rats and in ovariectomized rats hormonally primed with estradiol benzoate and progesterone. Drugs were administered systemically or by infusion into the vicinity of the ventromedial nucleus of the hypothalamus (VMN). By both routes of administration, inhibition of lordosis behavior was seen following treatment with the 5-HT 2A/2C antagonists, but the magnitude of the decline was smaller in proestrous than in hormone-primed, ovariectomized rats. The results of these studies are discussed in terms of the dual role of serotonin in the control of female sexual behavior.

Effects of acute and chronic administration of the antidepressants, imipramine, phenelzine and mianserin, on the social behaviour of mice

Effects of imipramine, phenelzine and mianserin on the behaviour of male CDl mice were examined after a single intraperitoneal injection (imipramine, 15.8 and 63.2 μmol/kg; phenelzine, 1 and 8μmol/kg); mianserin, 0.12 and 0.48 μmol/kg) and after administration for 12–16 days in the drinking fluid (mean daily intake; imipramine, 15.8 and 63.2 μmol/kg; phenelzine, 1 and 8 μmol/kg; mianserin, 0.12, 0.48 and 1.92 μmol/kg). Behaviour was examined by ethological procedures during 5 min encounters with an untreated partner in a familiar situation, the animal's home cage, and in the more aversive environment of an unfamiliar cage. At 30 min after injection, the higher doses of acutely administered imipramine and mianserin decreased aggressive behaviour in the unfamiliar cage. In the home cage, effects of mianserin were only slight, whereas imipramine reduced social investigation at the larger dose and in both test environments decreased digging. Phenelzine increased social investigation in both environments. After chronic administration, each of the drugs increased social investigation in the neutral cage and home cage at some of the dose levels, indicating potential anxiolytic efficacy. Mianserin showed the additional effect of enhancing digging during tests in the neutral cage, which may correlate with its anxiolytic actions. Phenelzine was the only antidepressant to increase aggression during encounters in the neutral cage after chronic administration. The significance of these findings is discussed.

Potential Role of 5HT1C and/or 5HT2 Receptors in the Mianserin‐Induced Prevention of Anxiogenic Behaviors Occurring During Ethanol Withdrawal

A single dose of mianserin (a 5HT1C/5HT2 antagonist), administered 1 hr, 48 hr, or 7 days before testing, was evaluated for its efficacy in alleviating or preventing the occurrence of anxiogenic behaviors observed during ethanol withdrawal. Other behavioral experiments using selected drug interactions were conducted to examine whether the effect of mianserin was related to a long-term modification of 5-hydroxy-tryptamine (5HT) receptor function. Rats were fed a liquid diet containing 4.5% ethanol for 4 days. They were tested on the elevated plus-maze (EPM) 12 hr (acute withdrawal) and 5 days (protracted withdrawal) after the last ethanol dose. Ethanol withdrawal induced a pattern of "anxiogenic" behavior that consisted of reduced activity (total entries) and a reduced proportion of open arm activity. Mianserin, injected as a single dose given either 1 hr (0.16-5 mg/kg, ip) before testing or given (20 mg/kg, ip) on the morning of the 3rd day of ethanol administration, i.e., 48 hr and 7 days before testing, dose-dependently prevented or reversed the ethanol withdrawal induced reduction in open-arm activity. In contrast, the 5HT1C/5HT2 receptor agonist (+/- )-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl (DOl) did not affect behaviors in the EPM in ethanol-naive rats, nor in those undergoing ethanol withdrawal. However, although there was a marked tolerance to DOl-induced body shakes (a measure of 5HT2 function) during withdrawal, DOl reversed the action of mianserin in the EPM. The 5HT1 receptor agonist, 5HT2 receptor antagonist 1-naphthyl-piperazine (1-NP) reduced open-arm activity in ethanol-naive rats and this action was enhanced during withdrawal.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of mianserin in chronic idiopathic abdominal pain A pilot study

Mianserin is a tetracyclic antidepressant that has gained popularity in Europe owing to lack of anticholinergic side effects and good tolerability. Being a histamine-1 and -2 receptor antagonist and an alpha-2 receptor blocker suggests that it should be of particular value in somatoform gastrointestinal disorders. In an open trial mianserin was given for 6 weeks to 24 patients with chronic idiopathic abdominal pain of more than 2 years' duration. Patients with a diagnosis of depressive or anxiety disorders were excluded. Daily dosage varied from 90 to 120 mg. Other psychopharmacologic or analgesic medication was not allowed during the trial. Pain response was measured by means of the Clinical Global Improvement Scale and daily self-reporting. Five patients dropped out. Of 19 completers, 15 reported significantly reduced pain. Placebo-controlled studies are needed to validate these encouraging results.

Effects of mianserin in chronic schizophrenia

Hizuki Yasushi, Naofumi Kajimura, Shusaku Kai, Masatomo Suetsugi, Itsuko Ushijima and Michio Yamada: Effects of Mianserin in Chronic Schizophrenia. Prog. Neuro-Psychopharmacol. & Biol. Psychiat. 1992, 16 (4): 517–528. 1. 1. The efficacy of mianserin as a supplement in treating chronic schizophrenia was tested by monitoring the BPRS and plasma monoamine metabolites. 2. 2. Twenty inpatiencs with schizophrenia were administered fixed doses of neuroleptics throughout the study. 3. 3. A control BPRS scoring and blood sampling were done before mianserin administration. 4. 4. Fixed doses of 60 mg/day of mianserin for 2 weeks and flexible doses for 4 weeks were given orally in an open study for 6 consecutive weeks, and no treatment followed for 1 additional week. 5. 5. BPRS scoring was carried out once weekly, and blood samples were obtained after mianserin treatment. 6. 6. Both total BPRS scores and scores for negative symptoms were decreased by mianserin treatment as compared with the control values. 7. 7. 5-HIAA concentrations of both responding patients and nonresponding patients to mianserin were increased after medication; however, 5-HIAA values of responding patients were lower than those of nonresponding patients. 8. 8. HVA concentrations of the responding group were slightly increased by mianserin administration. 9. 9. There were no significant changes in MHPG levels between the two groups. 10. 10. These results suggest that the negative symptoms of schizophrenia are partly improved by mianserin treatment.

Subjective side effects of mianserin in relation to plasma concentrations of mianserin and desmethylmianserin.

The main purpose of the present study was to examine the possibility that plasma concentrations of mianserin and its metabolite, desmethylmianserin, might be predicted by recording subjective side effects. In 44 depressed patients, subjective side effects during 3 weeks of treatment with 30 mg of mianserin were evaluated by the UKU Side Effect Rating Scale, and their relationships to plasma concentrations of mianserin and desmethylmianserin were analyzed. There was no significant relationship between plasma concentrations of these compounds and the occurrence of mianserin-induced side effects, except for dryness of mouth during week one. Our study, therefore, suggests that it is difficult to predict plasma concentrations of mianserin and desmethylmianserin based on the occurrence of subjective side effects.

Mianserin‐induced 5‐HT2 receptor downregulation results in anxiolytic effects in the elevated plus‐maze test

AbstractSeveral agents that downregulate 5‐HT2 receptors produce anxiolytic effects in humans, but the role of 5‐HT2 receptor downregulation has been difficult to assess because of their other actions. To test the effects of pharmacological downregulation of 5‐HT2 receptors on exploratory behavior in the mouse, mianserin, a drug known to downregulate 5‐HT2 receptors after a single dose, was administered 30 min, 48 hr, or 18 days prior to testing in the elevated plus‐maze. Following testing in the elevated maze, the head‐shake response to 4‐iodo‐R‐(—)‐2,5‐dimethoxyphenylisopropylamine (DOI), a selective 5‐HT2/5‐HT1C agonist was assessed, and in a separate group of animals 5‐HT1A, 5‐HT1B, 5‐HT1C, β1,β2, and 5‐HT2 agonist and antagonist binding was quantified autoradiographically. Mianserin pretreatment resulted in a significant dose‐related anxiolytic effect in the elevated plus maze evidenced by increases in the percentage of entries to, and time spent on the open arms. Head‐shakes induced by DOI were also dose‐dependently decreased as a result of mianserin pretreatment. At this time, the binding of the 5‐HT2 receptor antagonist, 7‐amino‐8[125I]ketanserin was decreased by 50%. Binding of DOI to 5‐HT2 receptors was decreased by 46%, and to 5‐HT1C receptors was decreased by 53%, but no other changes were found in any of the other receptor types examined. These findings demonstrate that the 5‐HT2 receptor plays at least a permissive role in anxiety‐like behaviors, since an intact 5‐HT2 system is necessary for the full expression of the anxiety‐like response, but the role of 5‐HT1C receptor downregulation in the effects of mianserin cannot be ruled out at this time. © 1992 Wiley‐Liss, Inc.

Effects of Mianserin on Negative Symptoms in Schizophrenia

The efficacy of mianserin as a supplement in treating chronic schizophrenia was tested in 20 inpatients with schizophrenia who were receiving fixed doses of neuroleptics. Mianserin was given for six weeks with a starting dose of 60 mg/day. A brief psychiatric rating scale (BPRS) was completed before starting mianserin and thereafter BPRS scoring was carried out once weekly. The total BPRS score and the score for negative symptoms were decreased by mianserin treatment as compared to the pre-treatment values. Plasma 5-HIAA concentrations were increased after medication in both responding patients and nonresponding patients. However, the 5-HIAA values of responders were lower than those of nonresponders. Plasma HVA levels were slightly increased by mianserin in the responders. There were no significant changes in MHPG levels. These results suggest that the negative symptoms of schizophrenia may be improved by mianserin treatment.

Effects of antidepressants on the intraventricular conduction and the incidence of arrhythmias induced by programmed ventricular stimulation in the dog heart after myocardial infarction

The effects of mianserin, a tetracyclic antidepressant, and adinazolam, a new triazolobenzodiazepine which has antidepressant activity, on intraventricular conduction and the incidence of arrhythmias induced by programmed ventricular stimulation were studied in the dog heart after myocardial infarction and compared to the effects of amitriptyline, a standard tricyclic antidepressant. Amitriptyline at a dose of 1 mg/kg significantly slowed ventricular conduction in a frequency-dependent manner and at doses of 2 and 3 mg/kg significantly slowed ventricular conduction in infarcted ventricular myocardium. Amitriptyline also significantly slowed ventricular conduction in normal myocardium. Amitriptyline increased the incidence of ventricular arrhythmias induced by the programmed ventricular stimulation and prolonged the intraventricular delayed conduction resulting in re-entrant ventricular arrhythmia. On the other hand, mianserin and adinazolam at doses of 1-3 mg/kg had no significant effects on intraventricular conduction in infarcted and normal myocardium and on the incidence of arrhythmias induced by programmed ventricular stimulation. From these results, we can expect that mianserin and adinazolam may have a much lower cardiac toxicity than amitriptyline.

Effects of Mianserin on Human Sleep

Sleep EEG and nocturnal penile tumescence (NPT) were investigated in 6 healthy men during placebo and mianserin administration and after mianserin withdrawal. The results were assessed in a historical comparison with those previously obtained with clomipramine. With mianserin, REM sleep was suppressed slightly. However, the suppressive effect of mianserin on REM sleep--based on the historical comparison--was significantly weaker than that of clomipramine throughout all the drug nights. Accordingly, a rebound increase in REM sleep was not observed after withdrawal. Less suppressive effects on NPT and disturbance of sexual function with mianserin than with clomipramine were observed. We suggest that a correlation between the prolonging effect on REM latency and the clinical antidepressant effect is limited to some antidepressants.

Two tests in rats for antianxiety effect of clinically anxiety attenuating antidepressants.

The effects of mianserin, trazodone, amoxapine, maprotiline, and doxepin were assessed in punishment and pentylenetetrazol drug discrimination paradigms. These two procedures are used to identify antianxiety activity in rats. In the punishment procedure, misanserin produced an inverse dose-related increase in punished responding. The magnitude of the increase in punished responding with mianserin was comparable to that observed with the anxiolytic, buspirone. This effect was not observed with any of the other antidepressants tested. None of the antidepressants were found to be active in antagonizing the discriminative stimulus effects of pentylenetetrazol. In fact, at high doses there was a suggestion that the antidepressants may generalize to the pentylenetetrazol discriminative stimulus. Therefore, several antidepressants with purported clinical antianxiety activity, were not active in two procedures that detect antianxiety activity in rats.

The effect of chronically administered mianserin, 8-hydroxymianserin and desmethylmianserin on the 'open field' behaviour and brain noradrenaline metabolism in the olfactory bulbectomized rat.

The chronic effects of mianserin and two of its major metabolites on the behaviour of olfactory bulbectomized rats in the 'open field' apparatus were studied. When these compounds were tested at the same dose, only the parent compound was active in attenuating the hypermotility which the bulbectomized rat exhibited under these experimental conditions. Changes in the concentrations of noradrenaline and 3-methoxy-4-hydroxyphenylglycol (MHPG) were also determined in the amygdaloid cortex and mid-brain regions of the sham-operated and lesioned rats. Only mianserin reversed the reduction in the noradrenaline concentration which occurred in the amygdaloid cortex following bulbectomy; the changes in noradrenaline or MHPG in the mid-brain were not correlated with this behavioural effect of mianserin.