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Biomedical subjects

F S Halpern

Publications and source records attributed to F S Halpern.

12 recordsLinked to original sources
PubMed1979

Normal prolactin responses in tardive dyskinesia.

Tardive dyskinesia has been hypothesized to be caused by a neuroleptic-induced dopamine hypersensitivity in the nigrostriatal system. This study evaluated with dopamine antagonists the possibility that such dopamine hypersensitivity extends to the tuberoinfundibular dopamine (TIDA) system, which regulates, by inhibition, pituitary prolactin secretion. Plasma prolactin concentrations in six patients with tardive dyskinesia were assessed in four conditions: During chronic haloperidol therapy; serially after abrupt haloperidol withdrawal; while unmediated; and in response to an acute dose of 0.5 mg IM haloperidol. In all four conditions, prolactin responses did not differ from those observed in normal subjects and schizophrenic patients without tardive dyskinesia. It is concluded that there is no evidence for post-synaptic dopamine hypersensitivity in the TIDA-pituitary pathway in patients with tardive dyskinesia, consistent with other reports assessing hormonal responses to dopamine agonists in such cases. It is further suggested that neuroleptic-induced dopamine hypersensitivity does not occur in the TIDA-pituitary system in humans, since it was not manifest in these tardive dyskinesia patients who would be thought particularly prone to develop it.

Adult↗
PubMed1979

Dopaminergic factors in human prolactin regulation: a pituitary model for the study of a neuroendocrine system in man.

This study in normal male subjects further investigates the effects of dopaminergic-antidopaminergic interactions as manifested by the prolactin response to dopamine and neuroleptic drugs. Incremental doses of dopamine hydrochloride (4 microgram/min, 15 microgram/min, 60 microgram/min, 300 microgram/min) were infused at a constant rate over 90-120 min after a fixed dose of a neuroleptic drug (sufficient for about half of the maximal prolactin response) had been given IV. A dose of dopamine in the order of 15-60 microgram/min appeared to match the "loss" of endogenous dopaminergic inhibition due to the antidopaminergic effect of the neuroleptic drug. The lactotrophic cells of the pituitary gland are suggested to serve as a model in man for the study of some basic neurohormonal mechanisms.

Adult↗
PubMed1979

Behavioral and neuroendocrine effects of low dose ET-495: antagonism by haloperidol.

Low doses of the dopamine agonist ET-495 were administered to nonpsychotic volunteer subjects by slow intravenous infusion, followed by a bolus of 1.5--2.5 mg haloperidol. ET-495 caused progressive dysphoria and sedation (in some cases, light sleep), effects believed to be mediated by dopaminergic inhibition. However, ET-495 also elevated growth hormone and suppressed prolactin, typical responses to dopamine agonist activity. Haloperidol reversed both the sedation and prolactin suppression induced by ET-495. These findings suggest: (1) that the sedation and hormonal responses were produced by stimulation of dopamine receptors; (2) that neurotransmitter systems mediating behavioral and neuroendocrine regulation may have differential neuropharmacological characteristics.

Adult↗
PubMed1979

Diurnal variation in the response of plasma prolactin, cortisol, and growth hormone to insulin-induced hypoglycemia in normal men.

Plasma PRL, cortisol, and GH responses to a standard iv dose of regular insulin were studied during the morning and evening in seven normal young men. Hypoglycemia achieved during morning and evening in the same aubjects was equal. There was a substantially greater maximal increment in PRL in the evening compared to the morning (P less than 0.01). The peak levels of cortisol achieved in the morning and evening were equal, but the evening maximal increase was greater (P less than 0.05) because of the significantly lower evening basal cortisol level. Evening increases in GH were greater than in the morning in five subjects and were essentially the same in two subjects; for the group, the evening maximal increment in GH was significantly greater (p less than 0.05 after log transformation). Since serotonergic mechanisms appear to be involved in the PRL, GH, and cortisol responses to hypoglycemia, we suggest the possibility of a diurnal variation in hypothalamic serotonin activity which may partly mediate these differential diurnal hormonal responses to hypoglycemia (although other neurotransmitters may also be involved). The data on cortisol are discussed with regard to the reset hypothesis of feedback inhibition.

Circadian Rhythm↗
PubMed1978

Prolactin responses to neuroleptics in normal and schizophrenic subjects.

The prolactin response to neuroleptics can serve as an index of dopamine blockade in humans. Plasma prolactin increments to single doses of chlorpromazine, and prolactin decrements to single doses of levodopa, were similar in normal and schizophrenic subjects. Antischizophrenic drugs of all chemical classes stimulated prolactin release,while chemically related drugs and other psychotropic agents ineffective in schizophrenia did not. The prolactin response to neuroleptic therapy occurred in all patients, and tolerance did not develop. Within subjects, prolactin responses were graded according to neuroleptic dose, but the upper limit of sensitivity of the response curve was achieved at doses below the therapeutic range. Relative prolactin-stimulating potency in humans of chlorpromazine, thioridazine, trifluoperazine, butaperazine, and haloperidol correlated well with their relative clinical potencies.

Chlorpromazine↗
PubMed1978

Relation of plasma prolactin to clinical response in schizophrenic patients.

It has been suggested that, if dopamine antagonism is a necessary condition for the antischizophrenic action of neuroleptics, the prolactin response, as an index of dopamine blockade, would correlate with clinical response. Morning prolactin and clinical symptomatology were measured in 15 schizophrenic patients before neuroleptic therapy, and after three and six weeks of high-dose butaperazine or loxapine treatment. Prolactin levels were transiently elevated during the unmedicated admission period, probably reflecting a normal stress response. Prolactin increased in all patients during neuroleptic therapy. There was, however, no correlation between magnitude of prolactin changes and clinical response, probably because the prolactin response achieved a maximum at relatively low doses of neuroleptics.

Adult↗
PubMed1976

Dopamine receptor alteration in schizophrenia: neuroendocrine evidence.

Growth hormone (hGH) responses to centrally acting dopamine agonists were used as indices of CNS dopaminergic function in order to test hypotheses implicating dopaminergic alteration in the etiopathology of schizophrenia. Apomorphine, a direct acting dopamine receptor agonist, and L-Dopa, an indirect agonist dependent upon presynaptic conversion to dopamine for its action, both elicited elevations in plasma hGH in most young male schizophrenic- and control-subjects. A highly significant difference was seen between the distribution of hGH responses to apomorphine for schizophrenics and that for controls. Unusually high hGH response to apomorphine was seen in schizophrenics who subsequently failed to respond to neuroleptic therapy; intermediate hGH response was seen in controls; and low hGH response was seen in subsequent neuroleptic responders; differences in hGH response were statistically significant for all intergroup comparisons. No such differences were seen between responses of individuals to L-Dopa and to apomorphine. The findings suggest that the variability of hGH response to apomorphine is a reflection of dopamine receptor sensitivity, and that this variability may be an index of non-endocrine related dopaminergic sensitivity. They are consistent with hypotheses relating schizophrenia to alteration in dopamine receptors, although the type of receptor and the direction of alteration may be complex.

Adult↗
PubMed1975

Human growth hormone response to levodopa. Relation to menopause, depression, and plasma dopa concentration.

After ingestion of 500 mg of levodopa, postmenopausal women had significantly diminished human growth hormone (HGH) responses (mean, 4.6 ng/ml), as compared with those of age-matched men (mean, 9.1 ng/ml; P smaller than .05). The differences between the groups were not related to plasma dopa concentrations. The HGH responses to levodopa of age-matched unipolar and bipolar depressed men, and of unipolar depressed postmenopausal women, did not differ significantly from their respective normal control groups. Depressive illness of these types does not appear to affect the HGH response to levodopa, once the effect of the menopause is taken into account.

Adult↗