Einwirkung von Wasserstoffsuperoxyd auf Thebain, Morphin und dessen Äther

Freund, Martin; Speyer, Edmund

doi:10.1002/cber.191004303100

Cited by 28 publications

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“…The concentration of all drugs has been expressed in terms of the base. Morphine-N-oxide was prepared according to the method of Freund & Speyer (1910). Solutions for injection were freshly prepared each day by dissolving the MNO in 0.1 N HCl and adjusting to pH 5 with NaOH.…”

Section: Teratogenic Activitymentioning

confidence: 99%

“…They suggested that MNO was an intermediate metabolite in the breakdown of morphine. Earlier reports suggested that MNO was without analgesic activity (Freund & Speyer, 1910;Rosenthaler, 1933; Keil, Schmidt & Giinther, 1933;Anton, Theiss & Weissig, 1935;Braenden, Eddy & Halbach, 1955). However, Fennessy (1968) found it to have a weak analgesic activity which was markedly potentiated when it was administered with either amiphenazole or tacrine to rats and mice.…”

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confidence: 95%

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Some observations on the toxicology of morphine-N-oxide

Fennessy

Fearn

1969

Journal of Pharmacy and Pharmacology

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The intravenous and subcutaneous acute toxicities of morphine-Noxide (MNO) in mice were respectively 3.2 and 8 times less than that of morphine. Amiphenazole or tacrine reduced the acute toxicity of MNO but not that of morphine in mice. The chronic toxicity of MNO was examined in mice and rats. Daily oral doses of 100 mg/kg did not significantly affect growth or condition, or produce gross or microscopic lesions in mice treated for 3 weeks or rats treated for 3 months. No teratogenic effect of MNO or of bromolysergic acid diethylamide was observed in rats.Woo, Gaff & Fennessy (1968) identified morphine-N-oxide (MNO) in the urine of patients treated with morphine in combination with either amiphenazole (2,4-diamino-5-phenylthiazole) or tacrine (1,2,3,4-tetrahydr0-9-aminoacridine) but not after morphine alone. They suggested that MNO was an intermediate metabolite in the breakdown of morphine. Earlier reports suggested that MNO was without analgesic activity (Freund & Speyer, 1910;Rosenthaler, 1933; Keil, Schmidt & Giinther, 1933;Anton, Theiss & Weissig, 1935;Braenden, Eddy & Halbach, 1955). However, Fennessy (1968) found it to have a weak analgesic activity which was markedly potentiated when it was administered with either amiphenazole or tacrine to rats and mice. The potentiation of the analgesic action of MNO and its presence in urine after morphine was suggested to be due to impairment of metabolism of MNO in the liver by amiphenazole and tacrine.MNO may be of clinical interest as a metabolite of morphine or as an analgesic in its own right. We have examined its toxicology. E X P E R I M E N T A L Acute toxicitySwiss mice of either sex, about 25 g were randomly assigned to groups of 10; various doses of morphine, MNO, amiphenazole, tacrine or nalorphine, given subcutaneously, were randomly assigned to these groups and the mice dead in each group after 24 h were recorded. The LD50 values with 95% confidence limits were calculated (Litchfield & Wilcoxon, 1949).The intravenous LD50 values for morphine and MNO were also determined in normal mice and in mice pretreated 30 min before with amiphenazole, tacrine or nalorphine injected subcutaneously in doses corresponding to one-third and two-thirds of their subcutaneous LD50 doses. Subacute toxicityFemale Swiss mice, 4 weeks old, about 15 g, were randomly assigned to 3 equal

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Section: Teratogenic Activitymentioning

confidence: 99%

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confidence: 95%

Some observations on the toxicology of morphine-N-oxide

Fennessy

Fearn

1969

Journal of Pharmacy and Pharmacology

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“…The concentration of amiphenazole has been expressed in terms of the salt, and those of morphine, morphine-N-oxide and tacrine in terms of base. Morphine-N-oxide was prepared according to the method of Freund & Speyer (1910). Solutions for injections were made by dissolving it in 0.1 N-HCI with adjustment to pH5 with NaOH; they were freshly prepared on the day of each experiment.…”

Section: Drugsmentioning

confidence: 99%

“…Morphine-N-oxide has been reported to possess little or no analgesic activity (Freund & Speyer, 1910;Rosenthaler, 1933;Keil, Schmidt & Gunther, 1933;Anton, Theiss & Weissig, 1935). It is difficult, however, to evaluate these reports for they contain insufficient information concerning the species and numbers of animals used, the routes of administration and whether morphine-N-oxide was given as a solid, suspension or solution.…”

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The analgesic action of morphine‐N‐oxide

Fennessy

1968

British J Pharmacology

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The analgesic activity of morphine‐N‐oxide in mice and rats has been investigated and compared with that of morphine. Both morphine and morphine‐N‐oxide were more active when given subcutaneously than when given intraperitoneally. Given subcutaneously, morphine was 11–22 times more potent than morphine‐N‐oxide and when given intraperitoneally it was 39–89 times more potent. The potencies depended on the test situation and the species of animal used. In animals pretreated with amiphenazole or tacrine, the analgesic activities of morphine and morphine‐N‐oxide were increased. The potencies of these analgesic drugs given intraperitoneally were increased to a greater extent than were the potencies obtained by subcutaneous administration. A possible explanation for the increase in analgesic potency of morphine‐N‐oxide produced by pretreatment with amiphenazole or tacrine may be that morphine‐N‐oxide is rapidly inactivated in the liver and this inactivation is impaired by amiphenazole and tacrine.

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“…However, a few synthetics of this type are now known and have recently been investigated (14) in detail; their behavior towards alkaline hydrogen peroxide is quite different from that of porphyroxine. Furthermore, hydrogen peroxide is known to react with codeine, yielding both an N-oxide (15) and a dimolecular compound (16). One would therefore have expected to find these also among the final products in the reaction of hydrogen peroxide with porphyroxine, which is said to constitute the most important proof for the structure assigned to the alkaloid.…”

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confidence: 99%

THE SEARCH FOR PORPHYROXINE IN INDIAN OPIUM¹

Rajagopalan¹

1945

J. Org. Chem.

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Einwirkung von Wasserstoffsuperoxyd auf Thebain, Morphin und dessen Äther

Cited by 28 publications

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Some observations on the toxicology of morphine-N-oxide

Some observations on the toxicology of morphine-N-oxide

The analgesic action of morphine‐N‐oxide

THE SEARCH FOR PORPHYROXINE IN INDIAN OPIUM¹

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Einwirkung von Wasserstoffsuperoxyd auf Thebain, Morphin und dessen Äther

Cited by 28 publications

References 0 publications

Some observations on the toxicology of morphine-N-oxide

Some observations on the toxicology of morphine-N-oxide

The analgesic action of morphine‐N‐oxide

THE SEARCH FOR PORPHYROXINE IN INDIAN OPIUM1

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THE SEARCH FOR PORPHYROXINE IN INDIAN OPIUM¹