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Decreasing sensitivity to neuroleptic agents in developing rats; evidence for a pharmacodynamic factor (1988)

Campbell, A. ; Baldessarini, R. J. ; Teicher, M. H.

Springer

Psychopharmacology 94 (1988), S. 46-51

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ISSN: 1432-2072

Keywords: Butyrophenones ; Catalepsy ; Development ; Haloperidol ; Maturation ; Perphenazine ; Phenothiazines ; Ptosis ; Rat

Source: Springer Online Journal Archives 1860-2000

Topics: Medicine

Notes: Abstract Developing rats are far more sensitive than adults to the behavioral effects of haloperidol. The present results support the hypothesis that this change may reflect age-related changes in brain responses such as alterations in drug-receptor or drug-effector mechanisms. Dose-response studies of catalepsy and ptosis were conducted in male Sprague-Dawley rats aged 30, 56, or 100 days. Resulting dose-effect curves were approximately parallel and showed rightward shifts with highly significant progressive increases of ED50. Similar developmental decreases in drug sensitivity (3–6 ×) were found following systemic (PO or IP) administration of haloperidol or the phenothiazine neuroleptic perphenazine, which differ markedly in structure, potency, distribution, and metabolism. Age-related decreases in drug sensitivity (3–4 ×) were also found using intracerebroventricular (ICV) administration of both agents in an attempt to bypass potential “pharmacokinetic” influences. Since the age-dependent decrease in sensitivity to both neuroleptics was found during the rising phase of drug action (1st hour) and ranked: PO〉IP〉ICV, some change in absorption and distribution of both drugs may occur in addition to the apparently important maturational decrease in target-organ sensitivity indicated by the responses to direct ICV injection and by the similarity of results obtained with dissimilar agents.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1007/BF00735879

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Pholasin chemiluminescence detects mostly superoxide anion released from activated human neutrophils (1989)

Müller, T. ; Davies, E. V. ; Campbell, A. K.

New York : Wiley-Blackwell

Journal of Bioluminescence and Chemiluminescence 3 (1989), S. 105-113

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ISSN: 0884-3996

Keywords: Human neutrophils ; chemiluminescence ; reactive oxygen metabolites ; superoxide anion ; Chemistry ; Biochemistry and Biotechnology

Source: Wiley InterScience Backfile Collection 1832-2000

Topics: Biology , Chemistry and Pharmacology

Notes: The bioluminescent oxygen metabolite indicator protein pholasin was characterized with respect to the type and location of reactive oxygen metabolites detected in suspensions of stimulated human neutrophils. Whereas pholasin detected reactive oxygen metabolites from neutrophil suspensions stimulated with soluble agents, particulate stimulants were apparently not effective triggering agents for pholasin-dependent neutrophil chemiluminescence. Neutrophils stimulated with fMet-Leu-Phe (1 to 100 nmol/l) showed maximum pholasin-dependent chemiluminescence 45 to 60s after stimulation. The time of maximum chemiluminescence was virtually independent of fMet-Leu-Phe concentration. In contrast, the time to reach maximum light emission increased from 60s with 100 nmol/l phorbol ester to 295s with 1 nmol/l phorbol ester. Significant inhibition of stimulated chemiluminescence was caused by both superoxide dismutase (20 μg/ml, 80% inhibition) and reduction of the oxygen concentration in the incubation medium to less than 0.5 μmol/l (95% inhibition). In contrast, the myeloperoxidase inhibitor sodium azide (0.1 nmol/l) afforded only 50% inhibition of the pholasin-dependent neutrophil chemiluminescence. Our results show that pholasin detects superoxide radicals released from cells stimulated by soluble stimulants but not intracellular oxidative activity elicited by particulate stimulants.

Additional Material: 3 Ill.