Comparative pharmacology of dothiepin, its metabolites, and other antidepressant drugs

@article{Heal1992ComparativePO,
  title={Comparative pharmacology of dothiepin, its metabolites, and other antidepressant drugs},
  author={David J. Heal and Sharon C. Cheetham and Keith F. Martin and John Browning and Graham P. Luscombe and R. James Buckett},
  journal={Drug Development Research},
  year={1992},
  volume={27}
}
The pharmacology of dothiepin and its human metabolites, northiaden, dothiepin sulfoxide, and northiaden sulfoxide, has been studied to determine whether the latter contribute to the therapeutic or side effects profile of the parent tricyclic antidepressant. In vitro, dothiepin was a potent noradrenaline and 5‐hydroxytryptamine (5‐HT) uptake inhibitor, while its secondary amine metabolite, northiaden, was selective for noradrenaline. However, the sulfoxide metabolites were almost inactive as… 
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Method Development and Validation for the Estimation of Dothiepin Hydrochloride by Using RP-HPLC in PURE and Tablet Dosage Form
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References

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Steady-State Serum Concentrations of Dothiepin and Northiaden after Two Dosage Regimens of Dothiepin Hydrochloride (Prothiaden)
TLDR
The study showed that the two regimens yielded similar steady-state serum concentrations both of drug and metabolite but inter-individual differences were large, with one exception, to be very similar after both regimens.
Correlation between plasma diphenhydramine level and sedative and antihistamine effects
TLDR
There was a positive correlation between plasma diphenhydramine level and sedative and antihistamine effects, but wide variation in the extent and rate of change of these effects were observed between the subjects.
Tricyclic antidepressant agents. I. Comparison of the inhibition of the uptake of 3-H-noradrenaline and 14-C-5-hydroxytryptamine in slices and crude synaptosome preparations of the midbrain-hypothalamus region of the rat brain.
TLDR
The role of protein binding and diffusion barriers in the causation of the difference in the results obtained with the two preparations is discussed.
Pirenzepine distinguishes between different subclasses of muscarinic receptors
TLDR
Binding studies using a new anti-muscarinic drug, pirenzepine, are used, in which heterogeneity of binding is found that correlates well with the pharmacological activity and cannot be taken as evidence for different receptor subtypes.
Metabolism and pharmacokinetics of dothiepin.
TLDR
Dothiepin S-oxide was the major metabolic reaching a peak level of 81(34-150) microgram/l at 5(4-6) h while that for northiaden was 33 (22-60) h.
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