學名: Mianserin Tablet (N.V.Organon)
商品名稱: Tolvon
生産商: N.V.Organon
機轉：
或是簡單中文描述如下：
Mianserin會抑制兩種腦部與控制食慾有關的化學成分，分別是serotonin和octopamine。Serotonin是用來告知腦部有食物的存在，而octopamine則是通知腦部飢餓的感覺。Mianserin會抑制serotonin和octopamine的受體，阻斷其通知腦部身體已經進食或是身體感到飢餓。
mianserin具阻斷突觸前α2-adrenergic阻斷作用，能促使catecholamine的釋放而治療憂鬱症。由於本身也具有阻斷histamine接受器的作用，因此與其他具鎮靜作用的藥物併用時，會產生藥物藥效學的交互作用，加強併用藥物的鎮靜作用。雖然目前仍未完全評估mianserin對於代謝酵素的影響為何，但一般認為mianserin較少有藥物動力學的交互作用
MECHANISM OF ACTION
1) Mianserin is a tetracyclic antidepressant which differs chemically and pharmacologically from tricyclic antidepressants. Mianserin combines presynaptic alpha-adrenergic receptor blocking activity with anti- histaminic and sedative properties, but has little or no central anticholinergic activity, and minimal effect upon central serotoningeric mechanisms (Brogden et al, 1978). Unlike tricyclic antidepressants, which block the uptake of norepinephrine and reduce its turnover, mianserin does not effect norepinephrine uptake and increases it turnover (Brogden et al, 1978; Goodlet et al, 1977).
2) EEG studies have indicated that mianserin has an EEG profile similar to that of amitriptyline (Fink et al, 1977; Fell et al, 1973; Itil et al, 1972). The unique quality of mianserin which differs greatly from tricyclic antidepressants, is that the drug is less likely to cause cardiotoxicity, anticholinergic effects (and possibly seizures), than tricyclic antidepressants. Overdosage of mianserin does not produce the severe complications observed with tricyclic antidepressants (convulsions, cardiac arrhythmias, respiratory depression, severe hypotension) (Crome et al, 1978; Crome & Newman, 1977).
3) The effect of mianserin on plasma levels of beta-endorphin immunoreactivity was studied in 8 depressed patients (Drago et al, 1982). Seven patients showed a decreased plasma level of beta-endorphin immunoreactivity and also showed improvement in symptoms assessed by a modified comprehensive psychopathological rating scale. The one patient who did not improve also had decreased beta-endorphin immunoreactivity plasma levels. The role of beta-endorphin in depression is unknown; however, this evidence indicates a possible link. Further research is needed to fully understand the relationship.
4) The anticholinergic and cardiovascular effects of mianserin in healthy subjects and subjects with cardiovascular disease have been reviewed (Kopera, 1983). Mianserin was devoid of anticholinergic and cardiovascular effects. Mianserin's effect on REM sleep was evaluated in 6 healthy males (Maeda et al, 1991). While REM sleep was suppressed during treatment, no rebound increase in REM sleep was observed after withdrawal of the drug. This data does not support the theory that antidepressant effect is associated with a rise in REM pressure.
5) Both mianserin and its enantiomers are pharmacologically active (Pinder & van Delft, 1983). A relationship has been found between plasma levels of the S(+) mianserin and improved scores on the Montgomery-Asberg Depression Rating Scale (Mihara et al, 1997). This suggests that the S(+) enantiomer may be responsible for the therapeutic effect. The side effect profile (sedation), may also be attributable to the enantiomers. Mianserin metabolites are also active; therefore response should consider mianserin and desmethylmianserin plasma concentrations. However, it has been suggested that the antidepressant effects of mianserin are due primarily to the parent compound rather than the metabolites (Hand et al, 1991). The dextroenantiomer does have a higher affinity for the 5-HT2 receptor.
6) Recently, differences were documented in enantiomer activity (Wood et al, 1993). In a rat model, it was found that (-) mianserin had a greater selectivity for the 5-HT3 reception, whereas, (+) mianserin showed greater selectivity for the 5-HT1C and 5-HT2 receptors.
2) EEG studies have indicated that mianserin has an EEG profile similar to that of amitriptyline (Fink et al, 1977; Fell et al, 1973; Itil et al, 1972). The unique quality of mianserin which differs greatly from tricyclic antidepressants, is that the drug is less likely to cause cardiotoxicity, anticholinergic effects (and possibly seizures), than tricyclic antidepressants. Overdosage of mianserin does not produce the severe complications observed with tricyclic antidepressants (convulsions, cardiac arrhythmias, respiratory depression, severe hypotension) (Crome et al, 1978; Crome & Newman, 1977).
3) The effect of mianserin on plasma levels of beta-endorphin immunoreactivity was studied in 8 depressed patients (Drago et al, 1982). Seven patients showed a decreased plasma level of beta-endorphin immunoreactivity and also showed improvement in symptoms assessed by a modified comprehensive psychopathological rating scale. The one patient who did not improve also had decreased beta-endorphin immunoreactivity plasma levels. The role of beta-endorphin in depression is unknown; however, this evidence indicates a possible link. Further research is needed to fully understand the relationship.
4) The anticholinergic and cardiovascular effects of mianserin in healthy subjects and subjects with cardiovascular disease have been reviewed (Kopera, 1983). Mianserin was devoid of anticholinergic and cardiovascular effects. Mianserin's effect on REM sleep was evaluated in 6 healthy males (Maeda et al, 1991). While REM sleep was suppressed during treatment, no rebound increase in REM sleep was observed after withdrawal of the drug. This data does not support the theory that antidepressant effect is associated with a rise in REM pressure.
5) Both mianserin and its enantiomers are pharmacologically active (Pinder & van Delft, 1983). A relationship has been found between plasma levels of the S(+) mianserin and improved scores on the Montgomery-Asberg Depression Rating Scale (Mihara et al, 1997). This suggests that the S(+) enantiomer may be responsible for the therapeutic effect. The side effect profile (sedation), may also be attributable to the enantiomers. Mianserin metabolites are also active; therefore response should consider mianserin and desmethylmianserin plasma concentrations. However, it has been suggested that the antidepressant effects of mianserin are due primarily to the parent compound rather than the metabolites (Hand et al, 1991). The dextroenantiomer does have a higher affinity for the 5-HT2 receptor.
6) Recently, differences were documented in enantiomer activity (Wood et al, 1993). In a rat model, it was found that (-) mianserin had a greater selectivity for the 5-HT3 reception, whereas, (+) mianserin showed greater selectivity for the 5-HT1C and 5-HT2 receptors.
或是簡單中文描述如下：
Mianserin會抑制兩種腦部與控制食慾有關的化學成分，分別是serotonin和octopamine。Serotonin是用來告知腦部有食物的存在，而octopamine則是通知腦部飢餓的感覺。Mianserin會抑制serotonin和octopamine的受體，阻斷其通知腦部身體已經進食或是身體感到飢餓。
mianserin具阻斷突觸前α2-adrenergic阻斷作用，能促使catecholamine的釋放而治療憂鬱症。由於本身也具有阻斷histamine接受器的作用，因此與其他具鎮靜作用的藥物併用時，會產生藥物藥效學的交互作用，加強併用藥物的鎮靜作用。雖然目前仍未完全評估mianserin對於代謝酵素的影響為何，但一般認為mianserin較少有藥物動力學的交互作用
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併用藥物
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交互作用機轉
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結果與處理方法
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HMG-COA reductase inhibitors (simvastatin,lovastatin) &SSRIs or nefazodone
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· SSRIs(fluoxetine)或nefazodone會抑制simvastatin及lovastatin經由CYP3A4代謝
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·升高simvastatin,lovastatin血中濃度，增加橫紋肌溶解症及肌炎發生率
·建議降低simvastatin,lovastatin使用劑量或換成pravastatin,fluvastatin,
atorvastatin(較少由CYP3A4代謝)
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Venlafaxine & antihypertension agents
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·高劑量venlafaxine會使血壓升高(dose dependent)
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·降低降血壓之藥效
·venlafaxine之劑量應緩慢調整
·監測血壓變化及調整降血壓劑之劑量
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Trazodone & amiodarone
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·trazodone具輕微心律不整之作用
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·可能引起心室性心律不整，造成QT波延長
·併用時應小心，必要時做心電圖檢查
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Mianserine & sedative compounds
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·Mianserine具阻斷histamine接受器之作用(藥物藥效學交互作用)
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·可能對鎮靜具加成作用
·用於老年人須注意過度鎮靜作用發生
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Nefazodone & CYP3A4 substrates
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·Nefazodone會抑制經由CYP3A4代謝之藥物，例如：alprazolam, triazolam, astemizole, cisapride
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·造成併用藥物血中濃度升高，特別是老年人
·小心評估可能發生之副作用
·改換不會抑制CYP3A4的抗憂鬱劑
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Mirtazapine &BZDs
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·Mirtazapine具阻斷histamine接受器之作用
(藥物藥效學交互作用)
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·加強BZDs的鎮靜作用
·老年人可能會出現過度鎮靜副作用
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Bupropion & lower seizure threshold agents
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·Bupropion會引起癲癇發作，若與phenothiazines或TCAs等會降低癲癇閥值的藥物併用，會增加癲癇發作
(藥物藥效學交互作用)
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·增加癲癇發作之危險性
·避免併用
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Bupropion & dopamine agonists
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·Bupropion具阻斷dopamine再吸回作用
·與Dopamine agonists產生藥物藥效學交互作用
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·增加激動、混亂、幻覺、噁心、嘔吐的副作用
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已報告過的副作用：
Bradyarrhythmia、Cardiotoxicity、Orthostatic hypotension、Ventricular arrhythmia、Erythema multiforme、Maculopapular eruption、Hyperglycemia、Hypophosphatemia、Isolated prolactin deficiency、Weight gain、Dysphagia、Excessive salivation、Glossitis、Agranulocytosis、Leukopenia、Arthritis、Restless legs syndrome、Delirium、Dyskinesia、Hyperactive behavior、Somnolence、Ototoxicity、Tinnitus、Decreased sexual function is described with the administration of mianserin (Kowalski et al, 1985a).
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