OPEN Foundation

X. Huang

Mood and neuropsychological effects of different doses of ketamine in electroconvulsive therapy for treatment-resistant depression


BACKGROUND: Treatment-resistant depression (TRD) is a growing clinical challenge. Electroconvulsive therapy (ECT) is an effective tool for TRD treatment. However, there remains a subset of patients who do not respond to this treatment with common anesthetic agent. Ketamine, a noteworthy anesthetic agent, has emerged as an augmentation to enhance the antidepressant efficacy of ECT. Trials of i.v. ketamine in TRD indicated dose-related mood enhancing efficacy. We aimed to explore anesthetic and subanesthetic concentrations of ketamine in ECT for TRD with respect to their impact on mood and neuropsychological effects.
METHODS: Ninety TRD patients (36 males, 54 females; average age, 30.6 years old) were randomly assigned to receive either ketamine (0.8mg/kg) (n=30), subanesthetic ketamine (0.5mg/kg) plus propofol (0.5mg/kg) (n=30) or propofol (0.8mg/kg) (n=30) as an anesthetic and underwent 8 ECT sessions. The primary outcome measures were the 17-item Hamilton Depression Rating Scale (HDRS-17), cognitive assessments and seizure parameters.
RESULTS: The ketamine group had an earlier improvement in HDRS-17, longer seizure duration, lower electric quantity, a higher remission rate, and a lower degree of executive cognitive impairment compared to the ketamine+propofol and propofol groups. The ketamine+propofol group showed earlier improvement in the HDRS-17, a longer seizure duration and a different seizure energy index when compared to the propofol group.
LIMITATIONS: The postoperative dissociative side effect was not assessed.
CONCLUSIONS: Both anesthetic and subanesthetic concentrations of ketamine have rapid mood enhancing actions in ECT for TRD, while anesthetic concentrations results in larger magnitudes of antidepression and cognitive protection. ECT with ketamine anesthesia might be an optimized therapy for patients with TRD.
Zhong, X., He, H., Zhang, C., Wang, Z., Jiang, M., Li, Q., … & Huang, X. (2016). Mood and neuropsychological effects of different doses of ketamine in electroconvulsive therapy for treatment-resistant depression. Journal of Affective Disorders, 201, 124-130.
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Iboga-Type Alkaloids from Ervatamia officinalis


Seven new iboga-type alkaloids, ervaoffines A–D (14), (7S)-3-oxoibogaine hydroxyindolenine (5), ibogaine-5,6-dione (6), and 19-epi-5-oxovoacristine (7), and 10 known alkaloids were isolated from Ervatamia officinalis. The absolute configurations of 17 were determined through X-ray diffraction and electronic circular dichroism (ECD) analyses. Ervaoffines A and B represent the first iboga-type pseudoindoxyl alkaloids in which the C-2 spiro carbon configuration is opposite to that of other members of this class, such as iboluteine (8). The relationship between the absolute configuration of the spiro carbons and the Cotton effect in the ECD spectrum is established for the first time for iboga-type pseudoindoxyl and oxindole alkaloids. Additionally, a plausible biogenetic pathway for these alkaloids is proposed.

Tang, B. Q., Wang, W. J., Huang, X. J., Li, G. Q., Wang, L., Jiang, R. W., … & Ye, W. C. (2014). Iboga-Type Alkaloids from Ervatamia officinalis. Journal of natural products, 77(8), 1839-1846.
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The Ketamine Analogue Methoxetamine and 3- and 4-Methoxy Analogues of Phencyclidine Are High Affinity and Selective Ligands for the Glutamate NMDA Receptor


In this paper we determined the pharmacological profiles of novel ketamine and phencyclidine analogues currently used as ‘designer drugs’ and compared them to the parent substances via the resources of the National Institute of Mental Health Psychoactive Drug Screening Program. The ketamine analogues methoxetamine ((RS)2-(ethylamino)-2-(3-methoxyphenyl)cyclohexanone) and 3-MeO-PCE (N-ethyl-1-(3-methoxyphenyl)cyclohexanamine) and the 3- and 4-methoxy analogues of phencyclidine, (1-[1-(3-methoxyphenyl)cyclohexyl]piperidine and 1-[1-(4-methoxyphenyl)cyclohexyl]piperidine), were all high affinity ligands for the PCP-site on the glutamate NMDA receptor. In addition methoxetamine and PCP and its analogues displayed appreciable affinities for the serotonin transporter, whilst the PCP analogues exhibited high affinities for sigma receptors. Antagonism of the NMDA receptor is thought to be the key pharmacological feature underlying the actions of dissociative anaesthetics. The novel ketamine and PCP analogues had significant affinities for the NMDA receptor in radioligand binding assays, which may explain their psychotomimetic effects in human users. Additional actions on other targets could be important for delineating side-effects.

Roth, B. L., Gibbons, S., Arunotayanun, W., Huang, X. P., Setola, V., Treble, R., & Iversen, L. (2013). The ketamine analogue methoxetamine and 3-and 4-methoxy analogues of phencyclidine are high affinity and selective ligands for the glutamate NMDA receptor. PLoS One, 8(3), e59334.
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