The inhibitory effect of trimethylamine on the anticonvulsant activities of quinine in the pentylenetetrazole model in rats

Department of Pharmacology, School of Medicine, Qazvin University of Medical Sciences, Qazvin, Iran.
Progress in Neuro-Psychopharmacology and Biological Psychiatry (Impact Factor: 3.69). 06/2008; 32(6):1496-500. DOI: 10.1016/j.pnpbp.2008.05.007
Source: PubMed


Quinine specifically blocks connexin 36 (Cx36), one of the proteins that form gap junction channels. Quinine suppressed ictal epileptiform activity in in vitro and in vivo studies without decreasing neuronal excitability. In this study, we considered the possible mechanism of anticonvulsant effects of quinine (1, 250, 500, 1000 and 2000 microM, i.c.v.) in the pentylenetetrazole (PTZ) model of seizure. Thus, we used trimethylamine (TMA) (0.05 microM, 5 microM, 50 microM), a gap junction channel opener, to examine whether it could reverse the effects of quinine in rats. Intracerebroventricular (i.c.v.) injection of quinine affected generalized tonic-clonic seizure (GTCS) induced by PTZ by increments in seizure onset and reducing seizure duration. Additionally, pretreatment with different doses of TMA (i.c.v.) attenuated the anticonvulsant effects of quinine on the latency and duration of GTCS. It can be concluded that quinine possesses anticonvulsant effects via modulation of gap junction channels, which could contribute to the control of GTCS.

6 Reads
  • Source
    • "From the point of view of GJ contribution to the neuronal synchrony, the most valuable research efforts are those where coupling between neurons was specifically blocked. Quinine has been used in a few studies, and was shown to block specifically those channels built from connexins Cx36 and Cx50 (Gajda et al., 2005; Nassiri-Asl et al., 2008). As connexin Cx50 is not expressed in the brain, local injection of quinine into brain structure blocks Cx36-GJs (Srinivas et al., 2001). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Electrical synapses are a type of cellular membrane junction referred to as gap junctions (GJs). GJs have been regarded as an important component within the neuronal networks that underlie synchronous neuronal activity and field potential oscillations. Initially, GJs appeared to play a particularly key role in the generation of high frequency oscillatory patterns in field potentials. In order to assess the scale of neuronal GJs contribution to field potential oscillations in the hippocampal formation, in vivo and in vitro studies are reviewed here. These investigations have shown that blocking the main neuronal GJs, those containing connexin 36 (Cx36-GJs), or knocking out the Cx36 gene affect field potential oscillatory patterns related to awake active behavior (gamma and theta rhythm) but have no effect on high frequency oscillations occurring during silent wake and sleep. Precisely how Cx36-GJs influence population activity of neurons is more complex than previously thought. Analysis of studies on the properties of transmission through GJ channels as well as Cx36-GJs functioning in pairs of coupled neurons provides some explanations of the specific influence of Cx36-GJs on field potential oscillations. It is proposed here that GJ transmission is strongly modulated by the level of neuronal network activity and changing behavioral states. Therefore, contribution of GJs to field potential oscillatory patterns depends on the behavioral state. I propose here a model, based on large body of experimental data gathered in this field by several authors, in which Cx36-GJ transmission especially contributes to oscillations related to active behavior, where it plays a role in filtering and enhancing coherent signals in the network under high-noise conditions. In contrast, oscillations related to silent wake or sleep, especially high frequency oscillations, do not require transmission by neuronal GJs.
    Frontiers in Neural Circuits 04/2014; 8:32. DOI:10.3389/fncir.2014.00032 · 3.60 Impact Factor
  • Source
    • "Research in animal models suggests that quinine may have antiepileptic properties.7–11 In rodent models, it reduces seizure duration10 and the expression of seizure discharges but does not influence basic electrocortical activity.9 "
    [Show abstract] [Hide abstract]
    ABSTRACT: BackgroundQuinine has anti-epileptic properties in animals. However, in humans this has not been systematically investigated.PurposeTo examine the available research evidence on the effects of quinine on seizures in adults or children.MethodsWe searched online databases for published and unpublished studies in any language from January 1966 to March 2011. We considered randomized controlled trials (RCTs) evaluating the use of quinine in comparison to other drugs in humans with malaria or other conditions, and that reported the prevalence of seizures. Random effects meta-analysis was used to pool effect estimates in order to determine the effect of quinine on the prevalence of seizures.ResultsWe identified six randomized controlled trials on severe malaria. Quinine was compared to the artemisinin derivatives in all trials. A total of 8,244 patients were included. In the meta-analysis, there was no significant effect of quinine on the prevalence of seizures when compared to the artemisinin derivatives (Odds ratio (OR) =0.90, 95% Confidence Interval (95%CI) =0.63-1.30). There was significant heterogeneity (I2=66%, Chi-square=17.44, p=0.008). Subgroup analysis showed that quinine significantly reduced seizures when compared to artemether (OR = 0.66, 95%CI = 0.49-0.88) but when compared to artesunate, prevalence of seizures increased significantly (OR = 1.24, 95%CI = 1.05-1.47).ConclusionThere is no sufficient evidence to conclude that quinine has any antiepileptic properties in humans.
    Annals of Neurosciences 01/2012; 19(1):14-20. DOI:10.5214/ans.0972.7531.180404
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In this study, the influences of the gap junction blocker quinine and the gap junction opener trimethylamine (TMA) in antinociception were examined using the formalin test as a model of pain. We found that quinine was dose-dependently antinociceptive in both the early and late phases of the formalin test. In contrast, TMA alone did not change the nociceptive threshold in the formalin test. In the both phases of the formalin test, TMA increased antinociception of quinine. It couldn't conclude that gap junction blockade plays role in the mechanism by which quinine suppresses pain responses in the formalin test. Furthermore, it seems that pretreatment with TMA has additive effects on the antinociceptive effect of quinine in the formalin test.
Show more