Alteration of norepinephrine metabolism with desipramine and zimelidine in depressed patients.

Twelve patients with a major affective disorder were treated during the depressed phase of their illness with desipramine hydrochloride and/or zimelidine hydrochloride, and urinary excretion rates of norepinephrine and its major metabolites were examined. During treatment with desipramine, daily urinary excretion of norepinephrine, 3-methoxy-4-hydroxyphenylglycol (MHPG), and vanillylmandelic acid was reduced, but urinary normetanephrine excretion was not significantly changed. In all patients, the proportion of urinary norepinephrine metabolites represented by normetanephrine was increased during desipramine treatment.

Plasma steady-state concentrations of hydroxylated metabolites of clomipramine.

Plasma clomipramine, desmethylclomipramine, 8-hydroxyclomipramine, and 8-hydroxydesmethylclomipramine concentrations were measured in nine obsessive-compulsive outpatients. The mean dose of clomipramine at steady state was 237.5 +/- 51.

High reverse T3 levels in manic an unipolar depressed women.

A relatively high percentage of patients with affective disorders have abnormalities of thyroid function, and over 60% of endogenously depressed and most manic patients show a blunted thyroid-stimulating hormone (TSH) response to thyroid-releasing hormone (TRH) injections. We now replicate earlier findings concerning relatively high 3,3',5'-triiodothyronine (reverse T3) levels in unipolar depressives and find similarly high levels in manic women. The significance of the present finding is unknown, but measurement of reverse T3 levels as a potential tool in differential diagnosis of affective disorders and in psychobiological research should be explored further.

High correlation of norepinephrine and its major metabolite excretion rates.

Twenty-four-hour urinary excretion rates of norepinephrine, normetanephrine, 3-methoxy-4-hydroxyphenylglycol, and (vanillylmandelic) acid were repeatedly measured in 12 depressed patients. High (greater than. 83) positive correlations were found between the excretion rates of these four substances.

Clorgyline. A new treatment for patients with refractory rapid-cycling disorder.

Five women with primary, major, bipolar affective disorder, characterized by rapid mood cycles and nonresponsiveness to conventional drug treatments, including lithium carbonate, were given low doses (2.5 to 10.0 mg/24 hr) of clorgyline, a selective inhibitor of monoamine oxidase type A.

Effect of low-dose clorgyline on 24-hour urinary monoamine excretion in patients with rapidly cycling bipolar affective disorder.

Effects of clorgyline on urinary excretion of norepinephrine, dopamine, tyramine, and their major metabolites, 5-hydroxyindoleacetic acid and phenylethylamine, were studied in four women who suffered from primary, bipolar affective disorder. All patients had rapid mood cycles and were nonresponsive to lithium carbonate. During placebo administration, a strong correlation was found between the excretion rates of norepinephrine and dopamine and their respective metabolites.

Fluctuating high urinary phenylethylamine excretion rates in some bipolar affective disorder patients.

Five women with primary major bipolar affective disorders had variable and at times very high urinary phenylethylamine (PEA) excretion rates. The clinical picture of these patients was characterized by periodic bizarre behaviors and short psychotic episodes. These patients were generally nonresponsive to the usual treatment modalities, and their symptoms were exacerbated by nonspecific monoamine oxidase inhibitors which further increased PEA excretion rates.

Zimelidine and norzimelidine protein binding measured by equilibrium dialysis and cerebrospinal fluid.

Steady-state concentrations of a new antidepressant, zimelidine (ZIM), and its active metabolite, norzimelidine (NZIM), were measured in plasma and cerebrospinal fluid (CSF) in eight depressed patients. Free drug, as calculated from the ratio of CSF to plasma concentration, of ZIM was 8.4 +/- 1.

Active metabolites of imipramine and desipramine in man.

Active hydroxy metabolites of imipramine (IMI) and desipramine (DMI) have been quantified in plasma and cerebrospinal fluid (CSF) from patients at steady-state. In plasma of prepubescent boys and adults the concentration of unconjugated 2-hydroxyimipramine is only 15% to 25% that of IMI; 2-hydroxydesipramine (OH-DMI) concentration, however, is usually 50% that of DMI and in some cases OH-DMI is the predominant compound. In CSF from adult patients the ratio of concentrations of OH-DMI/DMI is higher than in plasma.

Disparate serum thioridazine concentrations: liquid chromatography versus radioreceptor assay.

A radioreceptor and a liquid chromatographic assay quantitating serum thioridazine and its active metabolites yield widely disparate results. The difference between the results of the two assays was relatively random. Contrary to earlier suggestions the radioreceptor assay may not be suitable for the measurement of all neuroleptics particularly when a common reference, such as chlorpromazine, is used.

Altered hydroxydesipramine concentrations in elderly depressed patients.

Recent reports demonstrate that hydroxy metabolites of desipramine (DMI) have pharmacologic activity and do not just produce side effects. In patients treated with DMI, we determined the ratio of 2-hydroxydesipramine (2-OH-DMI) to drug at steady state. The ratios in the elderly patients were higher than in younger patients, and whereas plasma levels of 2-OH-DMI increased with age, urinary clearances decreased.

Concentrations of desipramine in elderly women.

Seven elderly depressed women were given desipramine, and plasma concentrations of the drug were measured from blood samples drawn after a single dose and during long-term use. The concentrations were no different from those found in younger patients. Aging does not seem to alter the plasma concentration of desipramine, and the authors conclude that the increased incidence and severity of the drug's side effects are probably not due to high drug concentrations.

In vitro interaction between bovine adrenal medullary cell membranes and chromaffin granules: specific control by Ca2+.

The control of the in vitro interaction between bovine adrenal medullary plasma membranes and chromaffin granules by calcium has been studied. This interaction, which has previously been shown to result in the release of the soluble granular content, is a possible cell-free model for exocytosis. The plasma membrane-induced catecholamine release was stimulated when the [Ca2+] exceeded 2x10(-7) M.

Tricyclic antidepressants do not alter thyroid hormone levels in patients suffering from a major affective disorder.

Abnormalities of thyroid function have been associated with affective disorders, and treatment with thyroid hormones or drugs that alter thyroid hormone levels can change the course of an affective disorder. Therefore, we investigated the possibility that mood-altering effects of tricyclic antidepressants would be mediated by alterations in thyroid hormones (T3 and T4) levels. In a group of 11 patients with affective disorders, tricyclic antidepressants did not alter serum T3 and T4 levels.

Methodological issues in the measurement of urinary MHPG.

Unlabelled: Reported mean values for urinary 3-methoxy-4-hydroxyphenylglycol (MHPG) for both depressed patients and controls vary substantially between laboratories. The present study describes methodological sources of variance affecting urinary MHPG values. Although intra-assay variance is small (coefficient of variation (CV) = 4.

Chronic effects of phasic middle ear pressure changes.

In an attempt to better define the mechanisms of barotrauma, middle and inner ear pathology was studied in guinea pigs three weeks following exposure to a brief, sudden middle ear pressure change. Findings included tympanic membrane perforations (particularly dependent upon high negative pressure exposures), vascular hemorrhage (primarily dependent upon high positive pressure exposures), serosanguineous effusions (predominantly dependent upon infection) and serous effusion (dependent upon negative pressure exposure). Round window perforations were common in high pressure animals with infection.