| Autor: |
LEVIER, DAVID G., BROWN, RONNETTA D., MUSGROVE, DEBORAH L., BUTTERWORTH, LEON F., MCCAY, J. ANN, WHITE, KIMBER L., HARRIS, LOUIS S., MUNSON, ALBERT E. |
| Zdroj: |
Fundamental & Applied Toxicology; Feb1995, Vol. 24 Issue 2, p275-284, 10p |
| Abstrakt: |
Previously, morphine has been shown to elevate corticosterone via the hypothalamic–pituitary–adrenal axis and to suppress the immune system. The present investigation sought to determine if the μ-opiate receptor agonist methadone incurred a similar immune suppression in B6C3F1 mice. Serum methadone and corticosterone levels peaked 1 hr following a single subcutaneous injection of 20 mg/kg methadone HCl. Indeed, the rise in corticosterone levels paralleled that of methadone. After a single injection with 20 mg/kg methadone a pharmacokinetic analysis revealed a serum half-life of ≈2 hr. Following five injections of methadone over a 24-hr period (every 6 hr), methadone levels were elevated as would be expected; however, corticosterone levels did not become elevated. This suggests that the ability of methadone to elevate corticosterone becomes uncoupled following repeated dosing, indicative of either a tolerance or an increased catabolic mechanism. Moreover, dosing every 6 hr for 5 days induced an increase in the catabolism of methadone itself. Therefore, all assays were begun 1 hr after subcutaneous administration of methadone HCl, a time at which both methadone and corticosterone serum levels were elevated. The primary IgM antibody response to sheep red blood cells (sRBC) was suppressed when splenocytes were immunized . In contrast, animals immunized with sRBC and assayed for the primary IgM antibody response 4 days later were not suppressed. The activity of the resident macrophages of the liver and spleen as measured by the uptake of C-sRBC was suppressed in a dose-dependent manner. Previously, it has been demonstrated that morphine suppresses hepatic and splenic phagocytic activity through an opiate receptor-mediated path way that involves the release of corticosterone. It would appear that methadone plays a similar role in the suppression of hepatic and splenic phagocytosis. [ABSTRACT FROM PUBLISHER] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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