Pharmacological and human studies with a highly potent opioid peptide, D-Met2, Pro5-enkephalinamide.

D-Met2, Pro5-enkephalinamide (DMPEA) is an opioid peptide having analgesic activity in animals more potent after intravenous administration than morphine. It is less toxic but in animals it showed a higher dependence capacity than morphine. Besides analgesia DMPEA produces in rodent behavioral symptoms similar to those evoked by morphine or beta-endorphin, resembling the actions of neuroleptica. In human trials DMPEA was found to produce unpleasant sensations, no euphoria, and sometimes even dysphoria. DMPEA increases the serum levels of prolactin, growth hormone and, to a less extent, of TSH. Those effect of DMPEA on pituitary hormones. Finally, the human studies indicated that DMPEA antagonized pain (measured with the submaximum effort tourniquet technique), but did not affect adversely and even improved attention and short-term memory; it had no effect on the long-term memory. As the subjective effects of DMPEA are not pleasant, and no patient desired to obtain another treatment, some optimism as to low habit-forming properties of DMPEA may be justified.

Effects of D-Met2, Pro5-enkephalinamide on pain tolerance and some cognitive functions in man.

The effects of D-Met2, Pro5-enkephalinamide (EA) on pain tolerance and some cognitive functions have been examined in healthy male volunteers. Dihydrocodeine (DC) was used as reference substance. Applying the submaximum effort tourniquet technique EA (10 mg SC) was found to elevate the pain threshold similarly to DC (20 mg SC). Neither DC nor EA impaired the performance in the symbol cancellation test, which quantitates the intensity of attention. In this assay rather a slight improvement was detected. in addition the short-term memory performance (Wechsler test) was also improved by EA and DC. No alteration was seen in the word fluency test, an indicator of long-term (semantic) memory. The data show that EA not only improves pain tolerance but some of its mental effects are similar to those of a classical morphine congener DC.

Human tolerability studies with D-Met2,Pro5-enkephalinamide.

As reported previously D-Met2,Pro5-enkephalinamide (EA) is a highly active enkephalin analogue. To examine its human tolerability male volunteers were treated s.c. with increasing doses (0.1-30.0 mg). The observed autonomic effects were as follows: feeling of heaviness in the limbs, dry mouth, pallor of the face and conjunctival injection. There was no significant change in blood pressure, pulse and respiratory frequency. The autonomic effects appeared within 15-30 min. However, its effects on mood and wakefulness i.e. slight drowsiness, decrease in psychic tension and emotional detachment developed only later. The serum prolactin level increased dose-dependently, while the growth hormone (HGH) content showed biphasic dose-response pattern. The TSH content increased only at the highest doses applied (10.0-30.0 mg).

Familially accumulated schizophrenia (folie à cinq) in association with Stein-Leventhal syndrome.

The authors describe the psychosis of both parents and their three daughters. The psychosis of the father and three daughters corresponds to the paranoid schizophrenias (more specifically, the affective paraphrenias), while the mother's psychosis is largely the result of induction. All 3 daughters suffer from surgically confirmed Stein-Leventhal syndrome. Such a close association of the two diseases cannot be by chance.

Clinical notes on the possible anticholinergic reversal of depressive syndromes.

The authors report on the effects of acute confusional states and deliria (pharmacogenic confusional syndromes - PCS), occurring under the influence of psychotropic drugs on the depressive syndrome of three patients. The favourable influence of PCS on the depressive syndrome is considered to be largely linked to the anticholinergic effect of the drugs. The observations made in these three patients may give support to the hypothesis that cholinergic activity has pathogenic significance in depressive syndromes.

Further data on the diagnostic value of spontaneous drawing.

In discussing 2 patients, the authors point out that a study of spontaneous drawings by psychotics can be of considerable diagnostic importance in clinical practice. The clear structure of the drawings threw doubt on the diagnosis of schizophrenia in the case of the first patient who could be classified in the schizophenia spectrum on the basis of the formal symptoms. In the case of the second patient, where th clinical picture suggested different diagnosis, the drawings represent the 'ossified' essence of the experience and behavior symptoms and thus provided an objective basis for nosological classification. In addition, a characteristic feature of the difference between the creativity of the schizophrenic and the creative artist could be seen from a comparison with medieval Gothic art.

[Proskinetic symptoms in motor psychosis as accentuating personality traits]. / Proskinetische symptome bei motilitätspsychose, als akzentuierende Persönlichkeitszüge.

Proskenetic symptoms have been observed by the authors in a study of motility psychosis. However, these proskinetic symptoms appeared to be a character trait of an infantile personality rather than a condition following as a consequence of psychosis. The question is raised as to whether proskinetic symptoms (and catatonic symptoms) may be considered accentuating personality traits.