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Biomedical subjects

L J Siever

Publications and source records attributed to L J Siever.

At least 163 records · Page 9Linked to original sources

Possible subsensitization of alpha 2-adrenergic receptors by chronic monoamine oxidase inhibitor treatment in psychiatric patients.

Clonidine was administered to nine psychiatric patients before and after chronic treatment (3 to 4 weeks) with clorgyline, a selective monoamine oxidase type A inhibitor with antidepressant efficacy. The hypotensive response to clonidine, believed to be mediated by brain alpha 2-adrenergic receptors, was significantly attenuated by chronic but not acute (2 to 3 days) clorgyline treatment, with a time course similar to the onset of its clinical efficacy. This study supports the hypothesis that subsensitization of alpha 2-adrenergic receptors plays an important role in clorgyline's antidepressant effects and may constitute a key contribution to the mode of action of other antidepressant treatments as well.

Adult↗

Growth hormone response to clonidine unchanged by chronic clorgyline treatment.

The growth hormone (GH) response to the alpha 2-adrenergic agonist, clonidine, was determined before and after chronic clorgyline treatment in 10 psychiatric patients. No significant differences emerged in the magnitude of the GH response to clonidine before as compared to after clorgyline. These results do not support the hypothesis that postsynaptic alpha 2-adrenergic responsiveness is enhanced following chronic antidepressant treatment.

Adult↗

The effect of amantadine on prolactin levels and galactorrhea on neuroleptic-treated patients.

Amantadine was given to 11 psychotic patients, concurrently on neuroleptic medications, who required treatment of neuroleptic-induced extrapyramidal side effects. Five of the 11 patients suffered from galactorrhea, and all of these reported improvement in their galactorrhea on amantadine. Plasma prolactin levels were measured in eight of the 11 subjects, and there was a significant decrease in these levels for the group. Presumably these effects are due to amantadine's properties as a dopamine agonist and suggest a possible use of amantadine in the treatment of neuroleptic-induced galactorrhea.

Adolescent↗

The dopamine system challenge in affective disorders: a review of behavioral and neuroendocrine responses.

The authors review studies of dopaminergic agents in affective disorder patients. Although evidence from cerebrospinal fluid studies, from the pharmacology of the antidepressants, and from several clinical trials implicates the dopamine system in the regulation of mood or activity level, as yet, no replicated study shows that affective level disorder patients are different from normals and their neuroendocrine response to the dopaminergic agents L-dopa and apomorphine. Some possible reasons for this apparent normality of neuroendocrine response are discussed.

Behavior↗

Presynaptic noradrenergic regulation during depression and antidepressant drug treatment.

A specific testable hypothesis in which supersensitive alpha-2-adrenoreceptors play an important role in the etiology and maintenance of affective illness is presented based on the following observations: (1) published findings of changes in adrenergic receptors in the periphery and brains of rats in response to antidepressant regimens; (2) new studies of the monoamine oxidase type A-inhibiting antidepressant clorgyline, specifically relating to adaptation in the alpha-adrenergic presynaptic negative feedback system; (3) human peripheral alpha-adrenergic receptor changes from studies of patients with affective illness; and (4) observations from animals and humans experiencing stress and withdrawal from chronic amphetamine and opiate administration, suggesting that the development of supersensitive alpha-2-adrenoreceptors may lead to affective illness in vulnerable individuals. Old and new pharmacologic treatments are then discussed in terms of their capacity to specifically alter adrenergic receptor state.

Animals↗

Genetic determinants of borderline conditions.

Evidence about the genetic determinants for borderline conditions is reviewed. The research data are too limited and the diagnostic practices followed in existing studies are too varied to allow firm conclusions to be drawn. Thus, the need for new studies starting with well-defined samples of borderline patients is clear. Previous work implicates genetic factors in the etiology of at least some borderlines, but it is unclear that borderlines by any definition will, as a group, have uniformly strong and specific genetic determinants. With further research, partially overlapping subgroups might be defined on the basis of careful examination of borderline patients' clinical characteristics and family histories. Such characterization could have potential clinical value since there may be subgroups of borderlines who respond differently to various psychopharmacologic treatments (Klein 1975) or to exploratory versus ego supportive psychotherapy (Stone 1977). Characterizations based on genetic considerations may have their limitations, since the genetics of these disorders probably involve complex interactions of a variety of factors that may be more or less specifically related to other major diagnostic groups.

Adoption↗

Second generation antidepressants: a comparative review.

The authors review four "second generation" antidepressants (maprotiline, amoxapine, trazodone, and nomifensine) in terms of action on biogenic amines and receptors, antidepressive efficacy, and adverse effects. Doxepin is used as a comparative agent and is similar to the prototypical tricyclic agents in all the above categories. Maprotiline is a selective noradrenergic agent, but shares a similar adverse effect profile with doxepin and may be associated with a high frequency of seizures in overdose. Amoxapine is a mixed action antidepressant with significant neuroleptic activity in vivo. Its adverse effect profile is highlighted by symptoms related to its neuroleptic activity, and seizures and acute renal failure in overdose. Trazodone is a selective serotonergic agent with low anticholinergic activity, and minimal morbidity/mortality in overdose. Reports of priapism, leading to impotence in some men, however, is of concern. Nomifensine is a potent noradrenergic and dopaminergic agent with low anticholinergic activity, and minimum cardiotoxicity and low morbidity/mortality in overdose. Its most important adverse effects include overstimulation and infrequent, usually reversible, immunologic hypersensitivity reactions. Trazodone and nomifensine have favorable profiles for use in the elderly. Trazodone may be more favorable in the anxious/agitated patient due to its sedative effects, whereas nomifensine may be more beneficial in the retarded, apathetic patient.

Aged↗

Overlap between borderline and schizotypal personality disorders.

Borderline personality was split into two diagnostic categories in DSM-III: borderline personality disorder (BPD) and schizotypal personality disorder (SPD). There remains a great deal of diagnostic overlap between these two categories despite modifications in DSM-III-R. This report discusses four possible hypotheses for this overlap: (1) an independent, random association; (2) artifactual overlap due to imperfections in the criteria sets; (3) a synergistic association of the two personality disorders; and (4) a manifestation of dimensional psychopathology. Empirical evidence for each of the first three hypotheses is weak and contradictory. Recent biologic and treatment studies appear to most strongly support the use of dimensional models of "borderline" and "schizotypal" personality traits.

Borderline Personality Disorder↗

Correlated cholinomimetic-stimulated beta-endorphin and prolactin release in humans.

Previous studies, both in animals and humans, have demonstrated that the intravenous or intraventricular administration of endogenous opioids and opiates produce dose dependent increases in plasma concentrations of prolactin. Notably, in humans, intravenous infusion of centrally active cholinomimetic drugs, such as physostigmine or arecoline, may produce significant increases in plasma concentrations of prolactin and beta-endorphin immunoreactivity. In three separate studies, conducted collaboratively between the National Institute of Mental Health and the University of California at San Diego, physostigmine and arecoline associated increases in plasma concentrations of beta-endorphin immunoreactivity were highly correlated with increases in plasma prolactin concentrations. These results are of interest because centrally active cholinomimetic drugs have been variously reported either to have no effect, to increase, or to inhibit anterior pituitary prolactin release. We propose that cholinergic stimulation of hypothalamic beta-endorphin may represent an interesting example of peptidergic modulation of primary neurochemical effects on hypothalamic-pituitary hormonal regulation.

Endorphins↗