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At least 19 recordsLinked to original sources
PubMed1997

The CYP2D6 genotype and plasma concentrations of mianserin enantiomers in relation to therapeutic response to mianserin in depressed Japanese patients.

The relationship between therapeutic response to racemic mianserin and steady-state plasma concentrations of S(+)- and R(-)-mianserin was studied in 26 Japanese patients with major depression. The daily dose of mianserin was 30 mg, and the duration of treatment was 3 weeks. Regarding S-mianserin, the proportion of responders (final Montgomery-Asberg Depression Rating Scale score of 10 or less) was significantly higher in the plasma concentration range of 10 to 23 ng/mL than outside (10 of 11 vs. 3 of 15, p = 0.0005). Such a plasma concentration difference between responders and nonresponders was not found for R-mianserin. In 15 patients, the relationships between the CYP2D6 genotype, determined by allele-specific polymerase chain reaction analysis and Escherichia coli RI restriction fragment length polymorphism, plasma concentrations of the enantiomers, and the therapeutic response were studied. Five patients were homozygous for the wild type (wt) allele (wt/wt), nine were heterozygous for the CYP2D6Ch (Ch) allele causing decreased CYP2D6 activity (Ch/wt), and one patient was heterozygous for the Ch allele and the defect allele CYP2D6D (D) (Ch/D). The Ch/wt group showed significantly higher plasma concentrations of S-mianserin (mean +/- SD: 15 +/- 6 vs. 8 +/- 1 ng/mL, p = 0.007) and proportion of responders (8 of 9 vs. 1 of 5, p = 0.023) than the wt/wt group. The patient with the Ch/D genotype had the highest plasma concentration of S-mianserin (37 ng/mL) and a poor response. No significant relationship was found between the CYP2D6 genotype and plasma concentration of R-mianserin. The study presented here thus suggests that the CYP2D6 genotype plays a major role in controlling plasma concentration of the S-enantiomer of mianserin, which contributes to a major extent to the antidepressant effect during mianserin treatment.

Adult↗
PubMed1994

Determination of the enantiomers of mianserin, desmethylmianserin, and 8-hydroxymianserin in the plasma and urine of mianserin-treated patients.

An HPLC method is presented which allows the measurement in the same run of the enantiomers of mianserin, desmethylmianserin, and 8-hydroxymianserin in plasma and urine of mianserin-treated patients. Limits of quantitation for the (S)- and (R)-enantiomers of mianserin and desmethylmianserin were 4 and 2.5 ng/ml, respectively, in plasma, and for the (S)- and (R)-enantiomers of mianserin, desmethylmianserin, and 8-hydroxymianserin 5, 2.5, and 5 ng/ml, respectively, in urine. The measured ratios of (S)-mianserin/(R)-mianserin and (S)-desmethylmianserin/(R)-desmethylmianserin in the plasmas of 10 mianserin-treated patients, all extensive metabolizers of debrisoquine as determined by CYP2D6 genotyping, varied, respectively, from 1.0 to 4.06 and from 0.19 to 0.64. As the enantiomers of mianserin differ in their pharmacological profile, these results could partially explain why, until now, no consistent relationship has been established between the therapeutic response and total [(S) + (R)] plasma levels of this antidepressant.

Adult↗
PubMed1992

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.

Adult↗
PubMed1993

Prediction of plasma concentrations of mianserin and desmethylmianserin at steady state from those after an initial dose of mianserin.

The relationships between the plasma concentrations of mianserin and desmethylmianserin at 18 h after initial dosing and those at steady state were studied in 19 depressed patients receiving 30 mg of mianserin at bedtime. Significant linear relationships were observed for mianserin, desmethylmianserin, and mianserin plus desmethylmianserin. The present study thus suggests that the plasma concentrations of these compounds after an initial dose of mianserin can be used for the prediction of an optimal dose.

Adult↗
PubMedDate not supplied

Cardiovascular tolerance of mianserin and interactions of mianserin with other drugs.

The presented data clearly show that mianserin, which is therapeutically equal to other antidepressants, is a drug with a new chemical structure, with a most probably different mechanism of action and with distinct advantages above comparative drugs. Mianserin has not only pronouncedly fewer anticholinergic and central side-effects but: a) apparently has no cardiotoxic effects neither on healthy subjects nor on depressive individuals nor on cardiac patients; b) doses not cause orthostatic hypotension; c) is devoid of adverse drug-drug interactions with coumarin-like anticoagulants, with sympathomimetic amines, with antihypertensive agents and shows but little and short lasting interactions with alcohol.

Anticoagulants↗
PubMed1980

[Behavioral pharmacology of mianserin hydrochloride, a new antidepressant (author's transl)].

Behavioral pharmacological properties of mianserin (1,2,3,4,10,14b-hexahydro-2-methyldibenzol[c,f]pyrazino [1.2-a]azepine monohydrochloride) were investigated in comparison with imipramine (IMP) and amitriptyline (ATP). Mianserin antagonized reserpine-induced hypothermia but to a much lesser extent than IMP or ATP, and did not block the ptosis evoked by reserpine or tetrabenazine. Amphetamine-induced stereotyped behavior was significantly enhanced by both IMP and ATP, but not by mianserin. Unlike IMP or ATP, haloperidol-induced catalepsy in the rat was not blocked by mianserin. Like IMP or ATP, mianserin did not suppress the convulsions induced by bemegride or strychnine in the mouse, and or emetic action of apomorphine in the dog, while only mianserin did not block the convulsions evoked by electric shocks. Mianserin more strongly potentiated the anesthetic action of thiopental than did IMP. ATP showed strong muscle relaxant action and the impairment of coordinated motor activities both in mice and rats, in the inclinated screen test and rotarod test, while, like IMP, these actions of mianserin were significant only in the rat. Catalepsy was not induced nor was the righting reflex suppressed by mianserin. In the low spinal cat, mianserin did not depress the amplitude of extensor MSR. Moreover, the MSR inhibition induced by conditioning stimulation of ipsilateral cutaneous afferents and the MSR potentiation evoked by conditioning stimulation of contralateral saphenous nerve were unaffected by mianserin. The curious behavior of mice and rats was significantly and dose-dependently suppressed by mianserin, and tended to be suppressed by ATP, while an enhancement was seen with IMP in large doses. Mianserin was the most potent in suppressing the fighting behavior induced by long-term isolation of the mouse, and was the weakest in suppressing electric-stimulation-induced fighting behavior, compared with IMP and ATP. Mianserin showed no significant suppression of the muricide behavior of the olfactory bulbectomized rat, while IMP significantly suppressed it. No significant differences were observed among mianserin, IMP and ATP as to their actions on the conflict behavior and the shuttle-box type conditioned avoidance behavior of the rat. These results indicate that behavioral pharmacological actions of mianserin were not always the same as those of IMP and ATP. Therefore, mianserin may be a new antidepressant with mechanisms of action which differ from that of the usual tricyclic antidepressants.

Agonistic Behavior↗
PubMed1980

Effect of mianserin on noradrenergic transmission in the rat anococcygeus muscle.

1 The effects of mianserin on the accumulation of (-)-[(3)H]-noradrenaline and on contractile responses to field stimulation, exogenously applied (-)-noradrenaline, and to tyramine were studied in the rat anococcygeus muscle.2 Mianserin (10(-9) to 10(-5) M) and nortriptyline (10(-9) to 10(-5) M) inhibited the accumulation of (-)-[(3)H]-noradrenaline. In this aspect mianserin had a similar potency to nortriptyline, the most potent tricyclic antidepressant in inhibiting noradrenaline accumulation in this tissue.3 Mianserin 10(-9) or 10(-8) M alone had no effect on contractile responses to field stimulation and to (-)-noradrenaline but inhibited the responses to tyramine. The responses to field stimulation at low frequencies and to (-)-noradrenaline were potentiated by 10(-7) and 10(-6) M mianserin. It is suggested that the inhibitory effect mianserin has on neuronal accumulation is primarily responsible for these effects. Mianserin 10(-5) M inhibited responses to field stimulation and to (-)-noradrenaline.4 In the presence of nortriptyline (10(-6) M), the contractile responses to field stimulations were potentiated by mianserin (10(-8), 10(-7) and 10(-6) M), 10(-8) M being the most potent in this aspect. Mianserin 10(-8), 10(-7), 10(-6) and 10(-5) M had a similar inhibitory effect on responses to (-)-noradrenaline. In the absence of neuronal uptake, the potentiating effect of mianserin on responses to field stimulation may be due to antagonism at presynaptic alpha-adrenoceptors. In the presence of 10(-6) M nortriptyline, 10(-5) M mianserin abolished responses to field stimulation.5 Following incubation of the tissue in the presence of 6-hydroxydopamine (10(-3) M for 3 h), mianserin (10(-7), 10(-6) and 10(-5) M) nortriptyline (10(-7) and 10(-6) M) and phentolamine (5 x 10(-8) and 5 x 10(-7) M) inhibited contractile responses to (-)-noradrenaline. This illustrates the ability of these agents to inhibit the responses to noradrenaline at a postsynaptic site. The inhibitory effect was dose-related with nortriptyline and phentolamine; this illustrates the ability of these agents to antagonize postsynaptic alpha-adrenoceptors. The inhibitory effect observed with mianserin was not dose-related. This suggests that in addition to its reported ability to antagonize postsynaptic alpha-adrenoceptors, mianserin may have another post-synaptic action at the level of, or distal to, the alpha-adrenoceptor.6 These results illustrate that, in the rat anococcygeus muscle, mianserin is a potent inhibitor of noradrenaline accumulation and may be an antagonist at presynaptic alpha-adrenoceptors. Mianserin also inhibits the responses to exogenously applied noradrenaline in this tissue by an action or actions at the level of, or distal to, the postsynaptic alpha-adrenoceptor.

Animals↗
PubMed1994

Stereoselective disposition of mianserin is related to debrisoquin hydroxylation polymorphism.

The pharmacokinetics of mianserin and its main metabolite desmethylmianserin were studied in poor and extensive metabolizers of debrisoquin and of S-mephenytoin after a single oral dose of racemic mianserin. The debrisoquin metabolic ratio (MR) correlated significantly with area under the serum concentration-time curves (AUC) for (+/-)-mianserin and (+/-)-desmethylmianserin. Enantioselective high-performance liquid chromatographic analysis of mianserin showed that debrisoquin MR was related to AUC(0-12) for S(+)-mianserin (rs = 0.87; p = 0.001; n = 15) but not for R(-)-mianserin. The ratio between the AUC(0-12) for S(+)-mianserin and that for R(-)-mianserin was higher in poor metabolizers than in extensive metabolizers. Two extremely rapid extensive metabolizer subjects had the lowest mianserin S/R ratios. No differences in the pharmacokinetics of mianserin or desmethylmianserin were found between extensive metabolizers and poor metabolizers of S-mephenytoin. The study shows that the elimination of both mianserin and its main metabolite desmethylmianserin is dependent on CYP2D6 activity. Furthermore, the CYP2D6-dependent elimination of mianserin shows marked enantioselectivity for the more active S(+)-enantiomer of mianserin.

Administration, Oral↗
PubMed1981

Effects of mianserin, desipramine and maprotiline on blood pressure responses evoked by acetylcholine, histamine and 5-hydroxytryptamine in rats.

1 In rats anaesthetized with pentobarbitone, intravenous administration of desipramine (0.1 mg/kg), maprotiline (0.5 mg/kg) or mianserin (0.3-3.0 mg/kg) did not modify the blood pressure lowering effects of acetylcholine (0.25-1.0 micrograms/kg, i.v.) which were significantly reduced by atropine (3.0 micrograms/kg, i.v.). 2 Maprotiline and mianserin, like promethazine (0.1 mg/kg, i.v.), inhibited the vasodepressor responses evoked by histamine (2.5-10.0 micrograms/kg,i.v.). however, desipramine was inactive against histamine. 3 In pithed rats, the pressor effects of intravenous 5-hydroxytryptamine (5-HT: 5.0-20.0 micrograms/kg) were antagonized by mianserin (0.01-0.3 mg/kg, i.v.) and cyproheptadine (0.01 mg/kg) but were unaffected by maprotiline and desipramine. 4 In syrosingopine pretreated rats given mianserin 0.1 mg/kg, intravenously, 5-HT (20.0 micrograms/kg, i.v.) produced a significant fall in blood pressure which could be reduced by a large dose of mianserin (10.0 mg/kg, i.v.). 5 In conclusion, desipramine, maptrotiline and mianserin, in doses previously found to inhibit noradrenaline neuronal reuptake in the rat cardiovascular system, lack muscarinic receptor antagonist properties. Whilst maprotiline and mianserin blocked vascular histamine receptors, only mianserin (10.0 mg/kg, i.v.). 5 In conclusion, desipramine, maptrotiline and mianserin, in doses previously found to inhibit noradrenaline neuronal reuptake in the rat cardiovascular system, lack muscarinic receptor antagonist properties. Whilst maprotiline and mianserin blocked vascular histamine receptors, only mianserin, like cyproheptadine, was a potent antagonist of the 5-HT receptors that mediate increases in blood pressure in rats. Finally, the vasodepressor effects of 5-HT in syrosingopine pretreated rats given a small dose of mianserin were antagonized by a large dose of mianserin, suggesting that 5-HT may activate two distinct types of receptors in the rat.

Acetylcholine↗
PubMed2002

Influence of mianserin on some central effects of ethanol.

The interaction of mianserin with ethanol in central nervous system (CNS) was investigated. Mianserin was administered at a single dose of 5 or 20 mgkg(-1) i.p. or as daily injections in a dose of 2.5 mgkg(-1) given for 14 days. The influence of mianserin on acute ethanol toxicity (LD(50)), on ED(50) of ethanol in rota-rod test, on the duration of ethanol sleeping time as well as on spontaneous locomotor activity and ethanol-induced hypothermia was investigated. Moreover, the influence of mianserin administered in a dose of 10 mgkg(-1) i.p. on post-ethanol changes in the bioelectric brain activity (EEG) recordings in rabbits was also investigated. The electrodes were implanted into midbrain reticular formation (MRF), dorsal hippocampus (Hp) and frontal cortex (C). Mianserin administered as a single dose of 5 mgkg(-1) was found to decrease LD(50) of ethanol and its ED(50) in rota-rod test. Mianserin administered as a single dose of 5 or 20 mgkg(-1) prolongs ethanol sleeping time in mice but given daily for 14 days has no influence on this time. Mianserin-induced hypothermia was observed after administration of single dose as well as increase of ethanol-induced hypothermia after administration of higher dose (20 mgkg(-1)). Mianserin administered daily for 14 days had no influence on post-ethanol changes in body temperature. Single dose of mianserin 20 mgkg(-1) decreases locomotor activity in mice while repeated administration has no influence on locomotor activity. In contrast, both single dose and repeated administration of mianserin prevents increased locomotor activity of animals observed after ethanol (2.5 mgkg(-1)). Mianserin administered to rabbits (10 mgkg(-1)) induces increase of share of low frequency 0.5-4 cps and decrease of share of frequencies 4-7 and 7-10 cps in EEG recordings from MRF and Hp. The recordings from frontal cortex show increase of share of frequencies 10-13 cps. Ethanol increases the share of low frequencies in EEG recordings and decreases the share of fast frequencies. Mianserin increases its influence on fast frequencies.

Animals↗
PubMed1985

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.

Animals↗
PubMed1980

[Effects of mianserin on functions of ascending and descending monoaminergic systems, using experimental models (author's transl)].

Studies were carried out to evaluate the antidepressant action of Mianserin as related to noradrenergic and serotonergic systems. The actions of known tricyclic anti-depressants were comparatively investigated together with Mianserin (Organon). Self-stimulation behavior induced by stimulation of the posterior hypothalamus and substantia nigra was unaffected by Mianserin and imipramine, was suppressed with chlorpromazine and markedly enhanced by methamphetamine. The enhancement due to methamphetamine was suppressed by both Mianserin and chlorpromazine, and was potentiated by imipramine. Mianserin, imipramine and amitriptyline enhanced the rolling movements induced by methamphetamine in rats in which the nigro-striatal dopaminergic system was destroyed by the injection of 6-hydroxydopamine. The excitation induced by ldopa administration, of isocarboxazid treated mouse was enhanced by Mianserin in doses over 25 mg/kg and by imipramine or amitriptyline. The excitation of MK-486 treated mouse, induced by L-5HTP was suppressed by Mianserin, nortriptyline augmented the excitation. The head twitches induced by 5HTP were reduced to 1/10 in onset frequency by Mianserin, 1 mg/kg, p.o. The suppressive potency of amitriptyline in this model was less than 1/5 of that of Mianserin. The potentiation of the flexor reflex of hind limbs of the spinal rat induced by the pretreatment with isocarboxazid and l-dopa, 20 hours after the reserpinization, was markedly suppressed by Mianserin and amitriptyline, but unaffected by imipramine nor chlorimipramine. The potentiation of the extensor reflex of hind limbs of the spinal rat, induced 20 hours after the reserpinization by pretreatment with isocarboxazid and 5-HTP was suppressed by Mianserin, even in a low dose of 0.5 mg/kg, and by amitriptyline in a dose of 10 mg/kg. As far as monoaminergic mechanisms are concerned, the mode of antidepresant action of Mianserin is probably different from that of tricyclic antidepressants.

5-Hydroxytryptophan↗
PubMed1994

Stereospecific reversal of stress-induced anhedonia by mianserin and its (+)-enantiomer.

Chronic sequential exposure to a variety of mild unpredictable stressors has previously been found to depress the consumption of a dilute (1%) sucrose solution and to inhibit food-induced place preference conditioning. In the present study, using a simplified version of the mild stress procedure, the decreased sucrose intake was reversed by chronic (4 weeks) treatment with the atypical antidepressant mianserin. The racemic compound (+/-)-mianserin (5 mg/kg per day) and one of its enantiomers, (+)-mianserin (2.5 mg/kg) were effective in this model; a lower dose of (+/-)-mianserin (2.5 mg/kg), and the other enantiomer. (-)-mianserin (2.5 mg/kg), were ineffective. Vehicle-treated stressed animals were also subsensitive to food reward in the place conditioning procedure: normal place preference conditioning was reinstated by chronic treatment with (+/-)-mianserin (5 mg/kg) or (+)-mianserin, but not by the lower dose of (+/-)-mianserin (2.5 mg/kg) or by (-)-mianserin. Raclopride (100 micrograms/kg) reinstated the decrease in sucrose intake in stressed animals successfully treated with (+/-)- or (+)-mianserin. The results suggest that (+)-mianserin is the active enantiomer in reversing chronic mild stress-induced anhedonia, and further support the hypothesis of a dopaminergic mechanism of antidepressant action in this paradigm.

Animals↗
PubMed1977

Effects of mianserin, a new antidepressant, on the in vitro and in vivo uptake of monoamines.

1 The effects of mianserin and of selected tricyclic antidepressants were compared in a number of monoamine uptake models. 2 The ability of mianserin to block the noradrenergic neurone membrane amine pump of rabbit brain stem slices was comparable to that of imipramine and amitriptyline and less than that of desipramine and nortriptyline. Both mianserin and desipramine were competitive inhibitors of noradrenaline uptake in vitro. The effect of mianserin on noradrenaline uptake in vivo was studied both peripherally and centrally. The ability of 6-hydroxydopamine to lower rat heart noradrenaline levels was found to be very sensitive to inhibition by tricyclic antidepressants. Mianserin was active in this model. However, its ability to block the 6-hydroxydopamine-induced fall in rat heart noradrenaline concentration was appreciably less than that of the tricyclics studied. 3 Mianserin, like tricyclic antidepressants, was essentially devoid of effect on dopamine uptake both in vitro and in vivo. 4 The ability of mianserin to inhibit [3H]-5-hydroxytryptamine uptake by rat hypothalamic synaptosomes was appreciably less than that of the tricyclic antidepressants studied. Mianserin was essentially devoid of effect on rat brain 5-hydroxytryptamine uptake in vivo. 5 It is concluded that in certain situations large doses of mianserin may block noradrenaline uptake in vivo. However, in no way does mianserin rival tricyclic antidepressants in blocking monoamine uptake in vivo. The clinical efficacy of mianserin cannot be attributed to inhibition of monoamine uptake.

Animals↗
PubMed1985

Adrenoreceptor interactions of the enantiomers and metabolites of mianserin: are they responsible for the antidepressant effect?

Mianserin is a tetracyclic antidepressant whose postulated mechanism of action involves release of noradrenaline mediated via cortical alpha 2-adrenergic autoreceptor blockade. This property resides stereoselectively in the S(+)-enantiomer of mianserin, which is also more potent in behavioural tests indicative of antidepressant activity, and in the reversal of clonidine-induced effects. Cortical receptor binding studies have indicated that although a similar stereoselectivity prevails for the inhibition of both alpha 2-binding (clonidine) and alpha 1-binding (prazosin), mianserin and its enantiomers are more potent antagonists at alpha 2- than at alpha 1-binding sites. However, no stereoselectivity is apparent for the antagonism of cortical alpha 2-heteroreceptors controlling serotonin release. Following chronic administration, (+/-)- and S(+)-mianserin, but not the R(-)-enantiomer, produce functional supersensitivity at alpha 2-autoreceptors which is unaccompanied by changes in clonidine binding. Neither mianserin nor its enantiomers alter the sensitivity of alpha 2-heteroreceptors following chronic administration. Like mianserin and its S(+)-enantiomer, but unlike R(-)-mianserin and the 8-hydroxy metabolite, the desmethyl metabolite inhibits noradrenaline uptake in vitro. 8-hydroxymianserin and, to a lesser extent, desmethylmianserin release noradrenaline from cortical slices via alpha 2-autoreceptor antagonism, but only the 8-hydroxy metabolite blocks alpha 2-autoreceptors and alpha 2-heteroreceptors in synaptosomal preparations. It is likely that S(+)-mianserin, desmethylmianserin, and 8-hydroxymianserin contribute substantially to the overall facilitating effect of mianserin on noradrenergic transmission in vivo. As yet it is unclear whether this effect is exclusively responsible for the antidepressant activity of mianserin or whether the stereoselectivity also shown by the mianserin enantiomers towards serotonin receptors plays a complementary role.

Animals↗
PubMed1981

Pharmacodynamic studies on mianserin and its interaction with clonidine.

There is evidence that clonidine's hypotensive effect is reduced by the concurrent administration of tricyclic antidepressants. It has been proposed that this results from an interaction at alpha 2-receptors in the brain stem where clonidine acts as a relatively selective agonist and the tricyclic antidepressants as antagonists. Mianserin is an antidepressant with a tetracyclic structure and, although it has been reported to cause less cardiovascular disturbance, there is evidence that it also has alpha-adrenoceptor blocking effects. This study in 6 normotensive healthy male volunteers was designed to investigate a possible interaction between clonidine and the antidepressant mianserin. Administration of the first dose of 20 mg mianserin was associated with acute cardiovascular effects, notably transient postural hypotension, but no significant disturbance of heart rate or blood pressure was detected after 3 days continuous treatment with mianserin 20 mg tid. Following pre-treatment with mianserin or placebo the responses to a single oral dose of 300 micrograms clonidine were then assessed. The combination of mianserin and clonidine was not associated with any attenuation of clonidine's hypotensive effect, erect or supine, but there was significant attenuation of clonidine's supine bradycardic effect. There was no evidence that mianserin interfered with the ability of clonidine to diminish salivary flow, cause sedation, and reduce catecholamine output, but it was noted that mianserin itself had a very pronounced sedative effect. Mianserin alone had no significant effect on salivary flow. This short term study demonstrates that mianserin does not significantly interfere with the responses to a single oral dose of clonidine.

Adult↗
PubMed1988

Neurochemical and autonomic pharmacological profiles of the 6-aza-analogue of mianserin, Org 3770 and its enantiomers.

The neurochemical and autonomic pharmacological profile of 1,2,3,4,10, 14b-hexahydro-2-methyl-pyrazino[2,1-a]pyrido[2,3-c]pyrido[2, 3-c] [2] benzazepine [+/-)Org 3770) and the related antidepressant drug, mianserin, have been compared. The uptake of [3H]noradrenaline ([3H]NA) in vitro was weakly affected by (+/-)Org 3770 (pKi = 5.6) in contrast to mianserin (pKi = 7.4). Both (+/-)Org 3770 and mianserin facilitated the release of [3H]NA in slices of cortex. The effects of NA mediated by alpha 2-adrenoceptors on the release of both [3H]NA or [3H]serotonin ([3H]5-HT) were antagonized by (+)Org 3770 with pKi values of 8.4 and 8.1, respectively. However, (-)Org 3770 only antagonized the effect of NA on the release of [3H]5-HT (pA2 = 7.7). The binding of [3H]rauwolscine to alpha 2-adrenoceptors was inhibited by (+/-)Org 3770 and mianserin with identical affinity (pKi = 7.0), whereas the binding of [3H]prazosin to alpha 1-adrenoceptors was less potently affected by (+/-)Org 3770 (pKi = 6.4) than by mianserin (pKi = 7.1). A similar difference was found for alpha 1- and alpha 2-adrenoceptors in vas deferens of the rat. The binding of [3H]mianserin to 5-HT2 receptors was less potently blocked by (+/-)Org 3770 (pKi = 8.1) than by mianserin (pKi = 9.4) while the binding of [3H]mepyramine to histamine-1 receptors was more potently affected by (+/-)Org 3770 (pKi = 9.3) than by mianserin (pKi = 8.75). The binding of [3H]quinuclidinylbenzilate to muscarinic cholinergic receptors was blocked equally by (+/-)Org 3770 (pKi = 6.1) and mianserin (pKi = 6.3). Similar data on tryptamine-D, histamine-1 and muscarinic cholinergic receptors in isolated organs were obtained. A prominent role for the blockade of alpha 2-adrenoceptors in the therapeutic effects of mianserin and (+/-)Org 3770 in depression is suggested, probably excluding a role of inhibition of the uptake of NA.

Animals↗
PubMed1994

Serum mianserin and ageing.

1. Mianserin is a tetracyclic antidepressant with relatively few anticholinergic and cardiovascular side-effects. Its clinical efficacy is comparable to that of tricyclic antidepressants. It is widely used in Europe, especially in elderly outpatients. 2. In the present studies, the authors have evaluated the efficacy of mianserin as well as the effects of ageing and concomitant psychotropic drugs on serum mianserin concentrations in 169 depressive psychiatric inpatients. 3. In the patients the mean serum mianserin concentrations or their interindividual variations did not differ between the old, middle-aged, and young age groups. Furthermore, elderly women and men did not differ from each other for their dose-related drug concentrations. Neither were any differences found in serum mianserin concentrations between the older (> or = 75 years) and younger elderly (65-74). As is the case with TCAs, the co-administration of neuroleptics increased serum mianserin concentrations in the elderly. When comparing the therapeutic response and serum mianserin concentrations the authors found that the patients with good clinical improvement had higher mean serum mianserin concentrations than those without efficacy. 4. There seem to be no clinically important changes in the pharmacokinetics of mianserin with advancing age. The present results do not support the claim that the therapeutic profile of this drug is altered with advancing age. Mianserin can be regarded as an antidepressant with relatively few side-effects in the elderly.

Adult↗