No abstract available.
Animals ; Iproniazid* ; Monoamine Oxidase* ; Rats* ; Tyramine*

The psychotropic effects of the original psychotropics currently in use, such as chlorpromazine, iproniazide, imipramine, lithium, and clozapine, have been applied to clinical practice through fortuitous discoveries of their psychiatric side effects (PSE). The etiopathophysiology of various psychiatric disorders have been deduced from the action mechanism of original psychotropics, and the designed drugs which selectively act on those neurotransmitters involved in the therapeutic effects of the original drugs are being developed as novel drugs. Psychiatric side effects cannot be considered to necessarily anti-therapeutic, as seen throughout the history of psychopharmacology. The clinical and pathophysiological significance of PSE deduced from their analyses according to the psychiatric symptoms manifested as PSEs are as follows: 1) PSEs are manifested according to the biological characteristics of the patient across diagnosis. This reflects the lack of biological basis in the current diagnostic system. 2) Psychotropics are important as in vivo pharmacological probes or challenges which, upon administration, allow for the biological characterization of the patient brain, i.e. pharmaco-biological typing of the patient may be performed based on the patient responses to the agent (both therapeutic and adverse effects). Such data may be of importance in subsequent prescription of the patient. 3) The hierarchy of a psychiatric disorder may be modified by drug administration, converting the disorder into that of a lower rank and thus into what is more easily treated. 4) A pharmacological approach, rather than a diagnosis-based one, is required. Consequently, more research into the still unknown psychotropic effects of each psychotropic is desired. In the process, clinically significant psychotropic effects currently undefined from the point of diagnosis-based approach may be discovered.
Brain ; Chlorpromazine ; Clozapine ; Diagnosis ; Humans ; Imipramine ; Iproniazid ; Lithium ; Neurotransmitter Agents ; Population Characteristics ; Prescriptions ; Psychopharmacology

Monoamine oxidase inhibitors (MAOI) have been widely used as antidepressants. Recently, there has been renewed interest in MAO inhibitors. The activity-guided fractionation of extracts from Angelica keiskei Koidzumi (A. keiskei K.) led to the isolation of two prenylated chalcones, xanthoangelol and 4-hydroxyderricin and a flavonoid, cynaroside. These three isolated compounds are the major active ingredients of A. keiskei K. to inhibit the MAOs and DBH activities. Xanthoangelol is a nonselective MAO inhibitor, and a potent dopamine beta-hydroxylase (DBH) inhibitor. IC50 values of xanthoangelol to MAO-A and MAO-B were calculated to be 43.4 microM, and 43.9 microM. These values were very similar to iproniazid, which is a nonselective MAO inhibitor used as a drug against depression. The IC50 values of iproniazid were 37 microM, and 42.5 microM in our parallel examination. Moreover, IC50 value of xanthoangelol to DBH was calculated 0.52 microM. 4-Hydroxyderricin is a potent selective MAO-B inhibitor and also mildly inhibits DBH activity. The IC50 value of 4-hydroxyderricin to MAO-B was calculated to be 3.43 microM and this value was higher than that of deprenyl (0.046 microM) used as a positive control for selective MAO-B inhibitor in our test. Cynaroside is a most potent DBH inhibitor. The IC50 value of cynaroside to DBH was calculated at 0.0410 microM. Results of this study suggest that the two prenylated chalcones, xanthoangelol and 4-hydroxyderricin isolated from A. keiskei K., are expected for potent candidates for development of combined antidepressant drug. A. keiskei K. will be an excellent new bio-functional food material that has the combined antidepressant effect.
Angelica* ; Antidepressive Agents ; Chalcones ; Depression ; Dopamine beta-Hydroxylase ; Inhibitory Concentration 50 ; Iproniazid ; Monoamine Oxidase ; Monoamine Oxidase Inhibitors ; Oxidoreductases* ; Selegiline