Biomedical subjects
H M Emrich
Publications and source records attributed to H M Emrich.
Endorphins in psychiatry.
The evidence for stress activation of endorphinergic systems suggests a physiological role in endogenous analgesic and anti-anxiety regulation which would provide a reserve in emergency situations. The possibility of involvement of these systems in psychiatric illness arises from the psychotogenic and anxiolytic properties of some opiates. The endorphin-excess and -deficiency hypotheses of schizophrenia are reviewed in the light of naloxone's small but statistically significant antipsychotic action, and the activation of endorphinergic systems in the course of neuroleptic therapy. The hypothesis that endorphinergic deficiency may be present in endogenous depression is reviewed. Although alterations in beta-endorphin immunoreactivity measured peripherally and in CNS have not been substantiated, therapeutic trials using a mu-receptor agonist have shown promise of a rapidly-acting antidepressant effect. ECT is accompanied by increases in plasma beta-endorphin immunoreactivity.
Current perspectives in the pharmacopsychiatry of depression and mania.
The observation that opiates and endorphins exert euphorogenic effects in normal probands points to a possible involvement of endorphins in different types of affective disorders. There are several powerful arguments that the activation of particular central opiate receptors (e.g. by "opium cure", beta-endorphin, partial agonists, release of endorphins via electroconvulsion) exerts curative effects in endogenous depression. Results from a double-blind investigation of the possible antidepressant action of the opiate partial agonist buprenorphine in patients with endogenous depression revealed a strong antidepressant effect of this substance. A series of anticonvulsants, possibly acting via a GABA-ergic-like mechanism (valproate, dipropylacetamide, carbamazepine and oxcarbazepine), have recently been shown by different groups to possess antimanic and also, partially, antidepressant properties. Furthermore, a synergistic mode of action in the prophylaxis of manic episodes has been observed as concerns valproate and lithium. On the other hand, there is some evidence from both in vitro and in vivo animal experiments that chronic application of lithium results in a modification of the GABA-turnover. The present paper reviews the present state of knowledge concerning the concept of a GABA-dependent regulation of affective states.
Therapeutic effects of GABA-ergic drugs in affective disorders. A preliminary report.
A possible antimanic efficacy of the GABA-ergic anticonvulsant valproate was examined by use of a double-blind, placebo-controlled ABA design. A marked improvement was observed after valproate medication in a group of 5 acutely ill manic patients. Similar results were obtained in 7 trials examining the antimanic property of the keto-derivative of carbamazepine (oxcarbazepine) in 6 patients with acute mania, whereas no antimanic effect could be observed in a treatment with diazepam and with THIP. Combination of THIP and diazepam in another patient showed a slight antimanic effect. Additionally, a possible prophylactic effect of long-term treatment using valproate was examined. In 8 of 9 patients exhibiting a bipolar affective or schizoaffective psychosis, who did not properly respond to lithium treatment, a prophylactic effect of valproate medication could be demonstrated. The results point to the view that anticonvulsants, possibly due to GABA-ergic effects, may be beneficial in affective disorders.
Heroin addiction: beta-endorphin immunoreactivity in plasma increases during withdrawal.
Seven patients with heroin addiction were hospitalized and immediately withdrawn from opiates. Abstinence symptomatology was evaluated quantitatively by use of the Himmelsbach Score. Maximal intensity of withdrawal symptomatology was reached within 2 days. beta-Endorphin immunoreactivity in plasma was measured by use of a very sensitive radioimmunoassay with a low cross-reactivity (28%) against beta-LPH. A statistically significant increase of mean plasma beta-endorphin-like immunoreactivity during withdrawal could be demonstrated.
New drugs for mania?
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[New concept for therapy of manic and depressive disorders].
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Antidepressant effects of buprenorphine.
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[The EEG of patients with acute manic psychoses before, during and after treatment with high doses of d-propranolol and dl-propranolol (author's transl)].
Six manic patients, drug-free for at least 10 days, were treated with high doses (up to 3,000 mg/day, corresponding serum levels up to 1,600 ng/ml) of d-propranolol or dl-propranolol in a double-blind, placebo-controlled study. The EEG's of these patients were studied over a maximum period of 21 days. All 82 EEG's were normal, they showed neither epileptic patterns nor any other signs for hypersynchronisation, as a possible side-effect of propranolol, nor other abnormalities, due to the manic condition. Analysis by fast-fourier-transformation produced no difference between the effect of d-propranolol or dl-propranolol on EEG compared intra- and inter-hemispherically by power-spectra, cross-spectra, phase-differences and coherences. At high serum levels (more than 1,000 ng/ml) there was a corresponding increase of power and a drop in frequency of the alpha-activity, maximally--1.1 c/s, which probably depended on the serum level. This result is in agreement with the hypothesis of a direct antimanic effect of the drug and comparable to the clinical effect of lithium, which produces similar changes in EEG. A comparison of the propranolol-induced EEG changes with EEG changes usually induced by sedative drugs, contradicts the hypothesis that the antimatic properties of propranolol are caused by unspecific sedation.
Stress reactions and endorphinergic systems.
The discovery of the endorphins, a family of distinctive endogenous peptides possessing opiate-like activity, which appear to play a central role in the regulation of pain and other vegetative functions, prompted several investigations in animals and in man as to their possible role in stress phenomena. Several different strategies have been employed: Measurement of concentrations and release of endorphins in different brain areas, measurement of pain sensitivity and of different behavioral variables of animals before and after stress stimuli (with and without the application of the specific opiate antagonist naloxone), measurement of actual levels of endorphins in CSF and plasma of patients with different types of neuroses and psychoses. The present state of research in this field is summarized.
Possible antidepressive effects of opioids: action of buprenorphine.
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Clinical trial of des-tyrosyl-gamma-endorphin in mental illness.
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Analgesic and euphoric effects of high dose diazepam in schizophrenia.
Schizophrenics treated with high doses of diazepam (150-200 mg/day) showed marked analgesia besides certain antipsychotic effects. Euphoria was noticed in some of the patients. We hypothesized that influence on the endorphin metabolism might contribute to these clinical effects. Therefore, we measured pain threshold by three different methods before and during diazepam treatment. All patients exhibited a 1.5- to 2-fold increase of pain perception. Further, using a double-blind design, the opiate antagonist naloxone (30 mg i.v.) was administered. A significant decrease but not a complete block of the euphoric state and of analgesia was achieved. It is, therefore, concluded that other pharmacological properties of diazepam might be involved in the diazepam-induced euphoria and analgesia in man.
A possible role of opioid substances in depression.
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Endorphinergic systems and the response to stress.
Endogenous opioid peptides (EOPs) are extensively disturbed throughout the CNS and found in the CSF, pituitary, plasma and many peripheral organs of animals and man. Their intracerebroventricular administration produces a spectrum of morphinomimetic effects. Biochemical evidence for an acute stress-evoked release of brain, spinal cord and pituitary pools of EOPs has accumulated and the sensitivity of both adult and developing endorphinergic systems to chronic stress has been shown. EOPs are involved in the mediation of the elevations in nociceptive threshold, core temperature, exploration and grooming behaviour elicited by stress. A role in the attenuation of anxiety is also indicated. Finally an endorphinergic control of pituitary secretion and the activity of peripheral organs under stress has been demonstrated. EOPs are apparently of general importance in the response to stress in both animals and man.
Action of [Des-Tyr1]-gamma-endorphin in schizophrenia.
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Therapeutic effect of valproate in mania.
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