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Biomedical subjects

D Pickar

Publications and source records attributed to D Pickar.

At least 253 records · Page 14Linked to original sources
PubMed1981

Tyramine infusions and selective monoamine oxidase inhibitor treatment. I. Changes in pressor sensitivity.

The enhanced sensitivity to the pressor effects of tyramine, an indirect-aging sympathomimetic found abundantly in the diet, is a well-known potentially dangerous side effect occurring during treatment with commonly used non-selective monoamine oxidase (MAO) inhibitors. The effects of treatment with the selective MAO-A inhibitor clorgyline and the partially selective MAO-B inhibitors pargyline and deprenyl on tyramine's pressor effects were studied in depressed patients using an IV steady-state tyramine infusion technique. After 4 weeks of treatment, clorgyline produced a significantly greater increase in tyramine sensitivity in comparison to a medication-free baseline (29-fold) than did pargyline (12-fold) or deprenyl (1.7-fold). The pressor effects of tyramine were significantly prolonged after cessation of infusion during both clorgyline and pargyline, but not deprenyl treatment. These data from IV tyramine administrations suggest that intestinal MAO inhibition is not the major determinant of the enhanced tyramine pressor sensitivity produced by clorgyline and pargyline.

Blood Pressure↗
PubMed1981

Tyramine infusions and selective monoamine oxidase inhibitor treatment. II. Interrelationships among pressor sensitivity changes, platelet MAO inhibition, and plasma MHPG reduction.

The relationship between changes in IV tyramine pressor sensitivity accompanying selective monoamine oxidase (MAO) inhibitor treatment and estimates of MAO-A and MAO-B inhibition in vivo were studied. Reductions in platelet MAO activity provided an index of MAO-B inhibition, while changes in plasma 3-methoxy-4-hydroxyphenethylene glycol (MHPG) were used as an hypothesized reflection of MAO-A inhibition. Chronic treatment with the MAO-A inhibitor clorgyline and the MAO-B inhibitor pargyline showed significant inhibition of the alternate MAO enzyme as well, although this crossover effect was greater for pargyline than clorgyline. The MAO-B inhibitor deprenyl appeared to maintain the greatest degree of MAO inhibition selectivity in vivo. Tyramine pressor sensitivity changes accompanying administration of the MAO inhibitors were highly correlated with decreases in plasma MHPG (r = 0.92), supporting our previous data indicating the rank order of clorgyline greater than pargyline greater than deprenyl for enhancement of tyramine pressor sensitivity and, thus, suggesting that tyramine potentiation is primarily a function of MAO-A rather than MAO-B inhibition. Changes in plasma MHPG are suggested to provide a potentially useful clinical index of in vivo MAO-A inhibition.

Blood Platelets↗
PubMed1981

Naloxone effects on beta-endorphin, cortisol, prolactin, growth hormone, HVA and MHPG in plasma of normal volunteers.

8 mg of naloxone were administered IV to 14 normal volunteers in a placebo-controlled, double-blind experiment. Plasma levels of beta-endorphin, cortisol, prolactin, growth hormone, HVA and MHPG were determined before and 45 min after administration. Naloxone elicited significant increases in cortisol and MHPG but did not change plasma levels of the other compounds. In an additional experiment on two subjects, 20 mg of naloxone caused elevations of beta-endorphin as well as of cortisol. This parallel increase indicates that the linkage between the secretion of beta-endorphin and ACTH/cortisol may be dose-dependent. The increase in MHPG is in agreement with the hypothesized association of noradrenergic hyperactivity and opiate withdrawal.

Adult↗
PubMed1981

Effect of carbamazepine on CSF opioid activity; relationship to antidepressant response.

Carbamazepine, a drug useful in the treatment of trigeminal neuralgia and temporal lobe epilepsy, has recently been found to have positive psychotropic effects in patients with manic and depressive illness. The possible effect of carbamazepine on opioid activity in cerebrospinal fluid (CSF) were assessed in patients with affective disorders using a radioreceptor assay that detects total opioid binding activity. No effect of carbamazepine was noted on CSF total opioid activity, although conclusions about its possible effects on discrete opiate systems must await other methodologies. Initial medication-free levels of opioid activity were positively correlated with the degree of antidepressant response to carbamazepine.

Carbamazepine↗
PubMed1981

Relationship between urinary free cortisol and CSF opioid binding activity in depressed patients and normal volunteers.

We investigated the relationship between hypothalamic-pituitary-adrenal (HPA) activity, as measured by 24-hour mean urinary free cortisol (MUFC), and cerebrospinal fluid (CSF) opioid activity in patients with major affective disorder and normal volunteers. Among depressed patients, but not normal volunteers, mean 24-hour urinary cortisol values were significantly correlated with CSF opioid activity measured by radioreceptor assay, but were not significantly correlated with beta-endorphin immunoreactivity measured by radioimmunoassay. MUFC, as expected, was significantly higher in depressed patients than in normal volunteers. Mean values of CSF opioid activity and beta-endorphin immunoreactivity did not differ significantly in the two groups. The positive opioid-MUFC correlation found in the depressed group appeared to depend on patients who were cortisol hypersecretors. These data, using relatively crude measures of cortisol and opioid activity, are suggestive of a relationship between these two systems, particularly under "activated" conditions such as those observed in depression.

Adult↗
PubMed1981

Ethanol increases opioid activity in plasma of normal volunteers.

The effect of acute ethanol administration on plasma levels of beta-endorphin-immunoreactivity and opioid activity was measured in 4 normal volunteers. 60 min following ethanol consumption opioid activity levels, measured by radioreceptorassay, increased significantly with peak rises of more than 400%; levels of beta-endorphin-immunoreactivity did not change significantly. These results are compatible with the effect of the opiate-antagonist naloxone, reversing ethanol-induced coma.

Adult↗
PubMed1981

Pharmacological challenges to the endogenous opioid system in affective illness.

The discovery of an endogenous opioid system has been rapidly followed by animal studies suggesting its importance in neuroendocrine regulation and behavior. Abnormalities of these functions in affective illness suggest that evaluation of behavioral and hormonal responses following the clinical administration of opiate agonists or antagonists might yield information pertinent to the pathogenesis, diagnosis, and treatment of depression. However, initial double-blind controlled clinical studies have yielded little evidence to support this suggested involvement of the opioid system in affective illness. Acute administration of opiate agonists has sometimes yielded a mild antidepressant response in depression, and naloxone has occasionally been reported beneficial in mania. There is, however, little to suggest that these responses are specific to affective illness. A decreased prolactin response to morphine administration has been reported in depression, but is not direct evidence of opioid system dysfunction in depression since abnormal prolactin responses to other challenges in depression have previously been reported. The endogenous opioid system is actually multiple systems marked by distinct distributions of multiple endogenous opioid peptides and opiate receptor subtypes, as well as varying accessibility to drug administration. Future challenges in depression may rely upon the development of opiate agonists and antagonists with preferential binding to opiate receptor subtypes and preferential distributions to stress particular endogenous opioid systems. Opiate peptide challenges may well be administered intrathecally to overcome the blood-brain barrier. Opiate antagonist challenges will rely upon increasing doses of naloxone, up to 10 mg/kg, in order to increase the range of blocked endogenous opiate systems. Chronic administration of challenges has been a seldom used strategy but may be important in evaluation of the physiology of sensitization and tolerance to pleasure in affective illness.

Behavior↗
PubMed1981

Endogenous opioid activity and beta-endorphin immunoreactivity in CSF of psychiatric patients and normal volunteers.

The authors measured total opioid activity by radioreceptor assay in the CSF of 41 normal subjects and 89 unmedicated psychiatric patients, including schizophrenic, schizoaffective, depressed, and manic diagnostic groups. Schizophrenic men had significantly lower levels of opioid activity than the normal men, although these levels did not significantly differ from levels of other male patients. The authors observed higher opioid activity during mania than during depression in paired samples for 4 manic-depressive patients. beta-Endorphin immunoreactivity in a subsample of the same subjects was no different in the patient group than in the normal group, suggesting that the differences in CSF opioid activity between schizophrenic men and normal patients may be related to opioids other than beta-endorphin.

Adult↗
PubMed1981

Behavioral and biological effects of acute beta-endorphin injection in schizophrenic and depressed patients.

In this double-blind study, beta-endorphin, 4-15 mg, was administered intravenously to 6 schizophrenic and 4 depressed patients. There were neither significant differences in behavioral ratings between beta-endorphin and placebo for the overall group nor for either the schizophrenic or depressed subgroup. Clinical worsening and improvement were observed in individual schizophrenic patients. There was no evidence of late-appearing therapeutic effects in 4 schizophrenic patients rated for 5 consecutive days after placebo and drug infusions. In 1 patient 10 mg of beta-endorphin produced neuroendocrine effects comparable to those produced by 5 mg of intravenously administered methadone; in 2 other patients it produced large increases in circulating opioid activity as determined by radioreceptor assay. These biological data support the notion that parenterally administered beta-endorphin exerts significant opiate-like activity in vivo.

Adult↗
PubMed1980

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↗