Search PubMed⌕ Search

Biomedical subjects

D de Wied

Publications and source records attributed to D de Wied.

At least 109 records · Page 6Linked to original sources
PubMed1982

Antipsychotic properties of Des-enkephalin-gamma-endorphin in treatment of schizophrenic patients.

Animal experiments have shown that the gamma-endorphin fragment des-enkephalin-gamma-endorphin (DE gamma E; beta-lipotropin 66-77) is the shortest sequence with neuroleptic-like activity with potency comparable to des-tyrosine-gamma-endorphin. We postulated that DE gamma E may be an endogenous peptide implicated in psychopathologic disease, particularly schizophrenia. To investigate the purported antipsychotic action of DE gamma E, 23 patients with different types of relapsing schizophrenia were treated with DE gamma E dissolved in saline or placebo. Neuroleptic medication was continued during the experimental period. In the first single-blind trial, two patients were treated with 1 mg of DE gamma E and two with 10 mg of DE gamma E intramuscularly (IM) daily for ten days. In the second double-blind placebo-controlled trial 13 patients were treated with 3 mg of DE gamma E IM daily for ten days and six received placebo. Of the 17 patients treated with DE gamma E, two did not respond, 11 had a slight to moderate effect, and four responded markedly. No side effects were observed. The response to DE gamma E appeared to be negatively correlated with the dosage of neuroleptic medication and the duration of the last psychotic episode. These results support the hypothesis that disturbances in gamma-endorphin fragmentation might contribute to the pathogenesis of schizophrenic psychoses.

Adult↗
PubMed1982

Opposite interactions between alpha- and beta-endorphin fragments with dopamine mediated responses on the rat rectum in vitro.

Dopamine causes a dose-dependent contraction of the rat rectum in vitro followed by a relaxation. This contraction can be inhibited by apomorphine and phenylephrine. This inhibition can be attenuated by the beta-endorphin (beta E) fragments 2-17 (des-Tyr1-gamma-endorphin, DT gamma E) and 6-17 (des-enkephalin-gamma-endorphin, DE gamma E). beta E 6-17 seems to be the shortest sequence with full activity in this respect since a shorter fragment (beta E 10-17) was less effective. The atypical neuroleptics oxypertine, sulpiride, and clozapine, the classic neuroleptic haloperidol and metoclopramide have a similar action to DE gamma E. The peptides and atypical neuroleptics do not affect the dopamine response per se while the classic neuroleptics haloperidol and metoclopramide enhance the dopamine response. The effects of the alpha-type endorphins are opposite to those of the gamma-type endorphins, since des-Tyr1-alpha-endorphin (DT alpha E, beta E 2-16) and des-enkephalin-alpha-endorphin (DE alpha E, beta E 6-16) enhance the phenylephrine-induced decreased responsiveness to dopamine. Structure-activity studies revealed that the active moiety of the alpha-endorphin fragments probably resides in the 6-9 region. In addition the alpha-type endorphins directly inhibit the dopamine response. It is concluded that the rat rectum may be used to analyse neuroleptic-like action. In this model alpha- and gamma-endorphin fragments may directly or indirectly influence the interaction of dopamine with the rectum. Because of the strong similarities between the effects of gamma-type endorphins and that of neuroleptics the results support the purported neuroleptic-like action of gamma-type endorphins. The influence of alpha-type endorphins and gamma-type endorphins on the apomorphine or phenylephrine induced decreased responsiveness to dopamine, although opposite, seems to be mediated by an influence on different dopamine sensitive systems.

Acetylcholine↗
PubMed1982

Hla, and the response to treatment with gamma-type endorphins in schizophrenia.

In order to investigate whether genetic factors are involved in the response of schizophrenic patients to treatment with gamma-type endorphins, we typed 32 Dutch schizophrenic patients for the HLA-A, -B, -C and -DR antigens. The total patient group showed an increase of HLA-Bw4 and HLA-Cw1. A subgroup of 20 paranoid patients showed an increase of HLA-Cw1 and a significant heterogeneity for the HLA-C locus. In 16 patients who responded moderately or markedly to treatment with gamma-type endorphins, an increase of HLA-B15/Cw3 and a decrease of HLA-B17 were found as compared to 16 patients with no or a slight response. Moreover, HLA-B15 was particularly increased in those patients who responded markedly and remained free of psychotic symptoms for a period of at least 6 months after treatment with gamma-type endorphins (RR = 24.6, Puncorr. = 0.0015). Our results suggest that genetic factors coded for within the HLA region are associated with paranoid schizophrenia, and that HLA-B15/Cw3 is associated with a marked and prolonged response to treatment with gamma-type endorphins.

Endorphins↗
PubMed1982

The treatment of schizophrenic psychoses with gamma-type endorphins.

The pharmacological actions of gamma-type endorphins show similarities to those of the neuroleptics. Two fragments of gamma-endorphin (beta-LPH 61-77) were therefore tested in patients with schizophrenic and schizo-affective psychoses who had shown an insufficient response to neuroleptics. The fragments were DT gamma E (beta-LPH 62-77) and DE gamma E (beta-LPH 66-77). Some of the patients studied responded favorably to this treatment. A number of criteria of differentiation between responders and nonresponders are discussed. The influence of DT gamma E on the central DA metabolism differs from that of the neuroleptics. It is therefore conceivable that gamma-type endorphins represent a different principle of action. The therapeutic efficacy of these compounds lends support to the hypothesis that disorders of central endorphin metabolism may play a role in the pathogenesis of psychoses of the schizophrenic type.

Brain↗
PubMed1981

Endogenous hyperprolactinaemia enhances amphetamine- and apomorphine-induced stereotypy.

Rats with endogenous hyperprolactinaemia induced by pituitary homografts under the kidney capsule were more sensitive to amphetamine and apomorphine with respect to drug-induced stereotypy, while a normal response was noted in drug-induced changes of locomotor activity, rearing and grooming. It is suggested that postsynaptic dopaminergic receptors, probably in the nigro-striatal system, may become selectively supersensitive in the endogenous hyperprolactinaemic animals.

Amphetamine↗
PubMed1981

Gamma-melanotropin and brain function.

In view of the close structural similarity between the pro-opiocortin fragment, gamma-MSH, and ACTH/MSH-type peptides, the behavioural profile of gamma-MSH was explored. Attention was first focused on behavioural procedures in which ACTH/MSH-related neuropeptides have been found effective. It was found that gamma-MSH and ACTH-like neuropeptides had opposite effects on avoidance behaviour. In this respect the activity of gamma-MSH resembles that of opiate antagonists rather than that of beta-endorphin. Accordingly, ACTH(1-24) induced excessive grooming which is blocked by opiate antagonists and is attenuated by gamma-MSH. In addition, gamma-MSH injected into the periaqueductal grey matter of the brainstem of opiate-naive rats elicited symptoms reminiscent of those seen after opiate withdrawal. Gamma-MSH attenuated several effects of intracerebroventricularly administered beta-endorphin (e.g. antinociception, hypothermia, alpha-MSH release) and decreased the acquisition of heroin self-administration. Although gamma-MSH at rather high doses displaced naloxone from its specific binding sites in brain homogenates, it did not interfere with beta-endorphin-induced effects on in vitro muscle preparations (guinea-pig ileum; rat rectum). Interestingly, gamma-MSH induced relaxation of the rat rectum in vitro. It is postulated that gamma-MSH may attenuate beta-endorphin-induced effects by acting via gamma-MSH receptor sites (functional antagonism), although a pharmacological antagonism cannot be excluded as yet.

Adrenocorticotropic Hormone↗
PubMed1981

(Des-tyrosine1)-gamma-endorphin in schizophrenia: clinical, biochemical, and hormonal aspects.

The neuropeptide (des-tyrosine1)-gamma-endorphin (DT gamma E; beta-LPH 62-77) was given to 10 schizophrenic patients who had been free of neuroleptic medication for at least 3 weeks. DT gamma E was injected intramuscularly in a dose of 1 mg daily for 10 days following a double-blind placebo-controlled crossover design. In 4 of the 10 patients a pronounced antipsychotic effect was observed; in 3 a temporary or slight reduction of psychotic symptoms occurred; and in 3 no response was noted. DT gamma E led to decreased plasma levels of prolactin and in some patients to increased concentrations of homovanillic acid in cerebrospinal fluid (CSF). Neither plasma levels of growth hormone and cortisol nor CSF concentrations of 5-hydroxyindoleacetic acid were affected by DT gamma E. These data confirm that DT gamma E has antipsychotic properties in a number of schizophrenic patients and suggest an interaction between DT gamma E and central dopaminergic systems.

Adult↗
PubMed1981

Brain adrenocorticotrophin after adrenalectomy and sham-operation of rats.

The influence of adrenalectomy on the level of immunoreactive 18-24 ACTH extracted from hypothalamus, hippocampus and pituitary gland of rats was investigated. Brain ACTH was further characterized by fractionation by gel-permeation chromatography. Porcine 1-39 ACTH was exposed to synaptic plasma membranes in vitro in order to evaluate the role of metabolic conversion in changes of brain ACTH content. Removal of the adrenals, when compared with sham-adrenalectomy, resulted in a transient depletion of ACTH content in the anterior pituitary gland and the hippocampus, but not in the hypothalamus and the neurointermediate lobe. However, sham-adrenalectomy caused a transient reduction in levels of ACTH when compared with levels before operation in all tissues studied. The effects of adrenalectomy on hippocampal ACTH content persisted in hypophysectomized rats. Treatment of adrenalectomized rats with corticosterone failed to restore the reduced ACTH content when it was administered in doses that completely suppressed the release of pituitary ACTH. Adrenal steroids, however, may exert a direct effect on the metabolism of ACTH in the brain as judged from the in-vitro studies with porcine 1-39 ACTH exposed to a synaptosomal plasma membrane fraction of hippocampal tissue. The present study suggests that control of brain ACTH occurs independently of the control of pituitary ACTH release.

Adrenalectomy↗
PubMed1980

Behavioural actions of neurohypophysial peptides.

The neurohypophysial hormones vasopressin and oxytocin modulate memory processes. Vasopressin facilitates while oxytocin attenuates memory consolidation and retrieval. These influences are located in different regions of the molecules. Thus, the neurohypophysial hormones act as precursor molecules for neuropeptides involved in memory processes. The covalent ring structures of both vasopressin and oxytocin mainly affect consolidation, the linear parts, retrieval processes, while nearly the whole oxytocin or vasopressin molecule is needed for attenuation of consolidation and retrieval. Regional studies by microdissection techniques in combination with a sensitive radioenzymatic catecholalmine assay, indicate that vasopressin modulates memory processes by modulation of neurotransmission in distinct catecholamine systems. Recent experiments suggest that the influence of vasopressin on memory consolidation is mediated by the dorsal noradrenergic bundle via terminal regions of this bundle. Studies on the conversion of oxytocin in synaptosomal plasma membrane preparations of rat limbic brain suggest the possible generation of fragments with specific effects on memory processes. Regional differences in enzyme activity further substantiate the implication of oxytocin as a prohormone in this respect. Clinical studies support the evidence from laboratory findings that vasopressin is also involved in memory processes in man.

Amino Acid Sequence↗