Erythropoietin (EPO) is both hematopoietic and tissue protective, putatively through interaction with different receptors. We generated receptor subtype-selective ligands allowing the separation of EPO's bioactivities at the cellular level and in animals. Carbamylated EPO (CEPO) or certain EPO mutants did not bind to the classical EPO receptor (EPOR) and did not show any hematopoietic activity in human cell signaling assays or upon chronic dosing in different animal species. Nevertheless, CEPO and various nonhematopoietic mutants were cytoprotective in vitro and conferred neuroprotection against stroke, spinal cord compression, diabetic neuropathy, and experimental autoimmune encephalomyelitis at a potency and efficacy comparable to EPO.

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Zuclopenthixol acetate, 5%, in Viscoleo was administered IM to 19 acutely disturbed, psychotic patients in doses of 50-150 mg. Fifteen patients received one injection, whereas four of the patients had two or three injections, usually with intervals of 3 days. The zuclopenthixol concentrations in serum were measured in series of samples taken from each patient during a 3-day period following the injection. In patients given identical doses serum concentrations of about the same order were obtained. Significant and good correlations were found between dose and maximal serum concentration and between dose and area under the serum concentration curve. The average serum concentration curve obtained when adjusting the data to a 100 mg dose has a maximum of 41 ng/ml after about 36 h, decreasing to 15 ng/ml after 72 h. A dose of 50-150 mg zuclopenthixol acetate in Viscoleo appeared to be sufficient for controlling the symptoms for most acutely disturbed, psychotic patients. The frequency of side effects, including extrapyramidal reactions, was low and the adverse reactions mostly mild, indicating that the risks for severe complications generally might be minimal. With a rapid onset of action, few and mild side effects, good tolerability at the injection site, and a duration of effect of 2-3 days, zuclopenthixol acetate in Viscoleo appears to offer advantages compared to conventional neuroleptic treatment in patients in whom an acute, calming effect is desired.

Eighty-three acutely disturbed, psychotic patients were included in an open multicentre study. The aim of the study was to evaluate the clinical effect of zuclopenthixol acetate in Viscoleo (CPT-A). Each patient received from one to four intramuscular injections of CPT-A during the 6-day study period. The duration of action after one injection was between 2 and 3 days and doses from 50 mg to 150 mg were sufficient for most patients. Treatment with CPT-A caused a pronounced and rapid reduction of the psychotic symptoms. At the end of the 6-day test period the mean total score on BPRS in acute non-manic and exacerbated chronic patients was reduced by more than 50 per cent. In acute manic patients the mean total score on BRMS was reduced by 57 per cent already 1 day after injection. Rapidly after the injection of CPT-A a useful short-acting sedation can be expected, but the risk for oversedation even after a second injection is low. The frequency of unwanted effects, including extrapyramidal reactions, was low and the severity of symptoms was most often mild. With a rapid onset of action, a duration of effect of 2 to 3 days, and few and mild side effects, CPT-A offers advantages over the neuroleptic preparations conventionally used in the initial treatment of acutely disturbed, psychotic patients.