[STUDIES ON THE PHARMACOLOGICAL ACTIONS OF CORYDALIS. XII. THE EFFECTS OF OPTICAL ISOMERS OF TETRAHYDROPALMATINE (THP) ON THE CENTRAL NERVOUS SYSTEM].
1964; National Institutes of Health; Volume: 27; Linguagem: Inglês
Autores
K C Kin, Xing‐Hua Zhen, Bin Hsu,
Tópico(s)Pain Mechanisms and Treatments
Resumo(1) By means of the radiant heat method, intravenous injection of l-THP at 20 mg/kg to rabbits was shown to produce a marked analgesia, but that of 10 mg/kg only a very weak effect. Although 20 mg/kg or even larger doses of d-THP exhibited no analgesic effect, the smaller dose (10 mg/kg) could synergize the smaller dose of l-THP(10 mg/kg) to yield an analgesic action as potent as that produced by 20 mg/kg of l-THP alone. When 4 or 8 mg of THP was given intraventricularly, only l-THP revealed an analgesia, whilst d-THP caused a temporary excitement. Under the same conditions, morphine at a dose of 20μg(equal to 1/200—1/400 of that of THP)produced an excellent analgesia. (2) l-THP or dl-THP (40—50 mg/kg) significantly potentiated hexobarbital narcosis and reduced spontaneous activity in mice, and antagonized amphetamine-hyperactivity and -toxicity in aggregating mice, while d-THP exerted little effects. Fifteen mg/kg of l-THP potentiated the subthreshold dose of pentobarbital to induce sleep. No such potentiation was observed, when 15 mg/kg of d-THP or the same dose made up by mixing equal portions of d-THP and l-THP was used. Thus, l-THP is an effective central depressant, but d-THP is not. (3) In mice following premedication with β-phenylethylhydrazine sulfate 50mg,/kg twice at an interval of 16 hours, unlike reserpine, the sedative-tranquilizing effect of l-THP or THB was not altered. The reserpine reversal excitation was completely antagonized by l-THP, dl-THP, THB as well as chlorpromazine. However, the long-lasting sedative-tranquilization of reserpine could not be antagonized by pretreatmerit with l-THP or TttB in mice or rabbits. The above-mentioned experiments showed that the mechanism of sedative-tranquilization of l-THP and THB did not belong to reserpine-type; and d-THP did not reveal any effect. (4) During stimulating the central end of the superficial radial or peroneal nerve in cats paralyzed with suceinyloholine, the evoked potentials conducted from the midbrain reticular formation and hypothalamus were recorded simultaneously. Intravenous injection of 10--30 mg/kg of l-THP inhibited these evoked potentials for about 30—60 minutes; so did THB. d-THP produced little effect. It suggests that the central actions of THP and its analogs are probably associated with the inhibition of activating reticular system.
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