Mianserin

Mianserin is a H1 receptor inverse agonist and is a psychoactive agent of the tetracyclic antidepressant.

The pharmacokinetics of mianserin suppositories for rectal administration in dogs and healthy volunteers: a pilot study.[Pubmed:27190632]

J Pharm Health Care Sci. 2016 May 17;2:12.

BACKGROUND: We formulated Mianserin suppositories for the treatment of delirium and evaluated their pharmacokinetics by measuring plasma drug concentrations in dogs and healthy human volunteers. METHODS: Mianserin suppositories were prepared by a melting technique using Tetramide(R) tablets and Witepsol H-15 as the suppository base. Pharmacokinetics of this 30-mg Mianserin preparation were evaluated in three beagle dogs and three healthy adult males, in line with ethics committee approval. Plasma Mianserin levels were determined using gas chromatography-mass spectrometry. RESULTS: In dogs, the maximum plasma Mianserin concentration (Cmax) was 1.3 +/- 0.4 ng/mL, the time to Cmax (tmax) was 5.5 +/- 4.3 h, and the area under the plasma concentration-time curve from 0 to 24 h (AUC0-24) was 18.9 +/- 1.9 hng/mL. In humans, the Cmax was 14.6 +/- 6.3 ng/mL, the tmax was 8 h, and the AUC0-24 was 266 +/- 103 hng/mL. CONCLUSIONS: The current study characterized the pharmacokinetics of Mianserin suppositories in dogs and humans. As compared to oral administration, the suppositories produced a lower Cmax and a delayed tmax, although AUC0-24 values were comparable. It will be necessary to identify an appropriate dose that produces an adequate plasma Mianserin concentration for effective and safe clinical use. TRIAL REGISTRATION: UMIN000013853.

Quantum chemical study and isothermal titration calorimetry of beta-cyclodextrin complexes with mianserin in aqueous solution.[Pubmed:28090612]

Org Biomol Chem. 2017 Feb 1;15(5):1209-1216.

beta-Cyclodextrin (beta-CD) is studied as a carrier of the drug Mianserin (MIA). beta-CD with MIA adducts with 1 : 1 and 2 : 1 stoichiometry are investigated in vacuo and in water using quantum chemical methods: PM6 and B3LYP/6-31G(d,p). An effect of the dispersion correction GD2 and the basis set superposition error on the complexation energies is also evaluated. Additionally, the interaction between MIA hydrochloride and beta-CD in aqueous solution at 298.15 K is examined experimentally by isothermal titration calorimetry. Interaction parameters, such as the binding constant, enthalpy, entropy and Gibbs free energy, are presented. Analysis of the obtained data led to the following conclusions: the interaction of MIA with beta-CD is rather strong; there is no significant energetic difference between the 1 : 1 complexes of beta-CD with S-MIA and R-MIA enantiomers; the 2 : 1 (beta-CD : MIA) adduct is energetically more favorable than 1 : 1; the complex formation of MIA + beta-CD is enthalpy and entropy driven.

Traxoprodil augments the antidepressant-like activity of agomelatine but not of mianserin or tianeptine in the forced swim test in mice.[Pubmed:27371898]

Pharmacol Rep. 2016 Oct;68(5):960-3.

BACKGROUND: The main objective of our study was to evaluate the influence of traxoprodil on the activity of the atypical antidepressant drugs (agomelatine, Mianserin, tianeptine). METHODS: The forced swim test (FST) in mice was used to determine the antidepressant-like activity of the tested agents. Drugs levels in brain tissue were assessed by a high performance liquid chromatography method. RESULTS: Concurrent intraperitoneal administration of per se ineffective doses of traxoprodil (10mg/kg) and agomelatine (20mg/kg) shortened the immobility time of animals in the FST. The observed effect was associated with elevated brain levels of traxoprodil. Similar interaction was not detected for traxoprodil and Mianserin (10mg/kg) or tianeptine (15mg/kg). CONCLUSION: Traxoprodil-agomelatine interaction is pharmacokinetic in nature. A combination of these agents has a potential to become an interesting strategy in the treatment of depression.

Mianserin affects alarm reaction to conspecific chemical alarm cues in Nile tilapia.[Pubmed:27554252]

Fish Physiol Biochem. 2017 Feb;43(1):193-201.

In this study, I show that Mianserin, a chemical with serotonin and adrenoceptor antagonist activities, increases fish vulnerability to a potential predator threat, when prey fish must deal with this threat based on conspecific chemical alarm cues. For that, I evaluated whether Mianserin, diluted in the water, influences the behavioral responses of Nile tilapia (Oreochromis niloticus) to conspecific skin extract (chemical alarm cues). I found that, while Mianserin did not abolished antipredator responses, this drug mitigates some components of this defensive reaction. Thus, a potential decrease in serotonin and adrenergic activities reduces the ability of dealing with predators when perceiving conspecific chemical alarm cues.