Posted by SLS on January 1, 2001, at 21:26:25
In reply to Re: S.D.- some more thoughts » SLS, posted by judy1 on January 1, 2001, at 17:54:57
> Hi Scott,
> Thank you for the correct term- I was really thinking circadian, but then the insect kept coming to my mind.> I think this is a result of my head injury or too many drugs- both legal and nonlegal.
You cannot blame a head injury on this one. Just think how confused lexicographers must have been to have chosen the word "etymology" to label their scholarly studies when the word "entomology" popped into their heads.
> Anyway, yes I got manic on lamictal- actually they said I "overshot", which I rather like.
> To show my ignorance, when you said dopaminergic effects- does that mean an increase in dopamine?
I guess we both are to show our ignorance. I don't know if Lamictal specifically increases the amount of dopamine available to receptors. Over these last five years, I have felt that Lamictal was pro-dopaminergic; it enhances or increases the activity of dopaminergic neurons. This is in addition to the inhibition of glutamate release, which has been considered the most likely mechanism for producing its anticonvulsant (and mood stabilizing?) effects.
1. Lamictal produces tics in individuals with and without diagnosed involuntery movement disorders. This is phenomenon seen with disorders thought to be mediated through dopaminergic neurons and produced by Ritalin and amphetamines, pro-dopaminergic drugs, when they are used to treat things like ADD AD/HD.
2. Lamictal, unlike other "mood-stabilizers" has shown to infrequently produce mania, a state thought by many to involve an increase in dopaminergic neurotransmission.
3. Lamictal, unlike the other anticonvulsants, has shown a positive therapeutic effect in Parkinson's Disease, a disorder involving too little dopamine, when it is combined with l-dopa. This is a property shared with selegiline, a dopaminergic MAO-inhibitor. The inhibition of glutamate release by Lamictal has been discounted by several studies as being the mechanism by which it exerts its positive effects.
> And if that is the case, I thought that was implicated in positive psychotic symptoms.
It is. This might be why anti-dopaminergic drugs that block dopamine receptors are effective in treating positive symptoms.
> If I'm way off base, please let me know.
:-)
> Take care- JudyYou do the same- Scott
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1: Epilepsia 2000 Jul;41(7):862-7Lamotrigine-induced tic disorder: report of five pediatric cases.
Sotero de Menezes MA, Rho JM, Murphy P, Cheyette S
Department of Neurology, University of Washington School of Medicine, Seattle, Washington, USA. msoter@chmc.org
PURPOSE: To describe the clinical spectrum of lamotrigine (LTG)-induced tics (an uncommon side effect) in children. METHODS: Retrospective analysis of patients from our hospital-based practice who developed tics while on LTG. Data obtained from medical records, interviews with parents, video-EEGs, and homemade videotapes. RESULTS: Three males and two females (range, 2.5-12 years; mean, 6.9 years) developed a movement disorder within the first 10 months of therapy (maintenance doses, 4-17 mg/kg/day). Four patients exhibited simple motor tics; one patient experienced mostly vocal (i.e., gasping sounds) tics. Laryngoscopic evaluation of one 2.5-year-old with repetitive gasping sounds was normal. In three cases, tics resolved completely within 1 month of drug cessation; tics recurred in two of these patients after reintroduction of LTG. A fourth patient experienced gradual improvement after stopping LTG over 4 months; the fifth patient's simple motor tics improved spontaneously with a reduction in medication. None of the patients had clinical features of a neurodegenerative disorder, and none met diagnostic criteria for Tourette syndrome. Two patients, however, had a diagnosis of acquired epileptic aphasia syndrome, and one patient had nonprogressive expressive and receptive language dysfunction. A fourth patient had global static encephalopathy, and the fifth patient had only attentional problems. In all patients, tics were not associated with ictal EEG changes. CONCLUSIONS: LTG may infrequently induce simple motor tics, vocal tics, or both. Patients with severe language dysfunction may be particularly susceptible to this uncommon side effect. Further studies are necessary to clarify the population at risk.
PMID: 10897158, UI: 20357679
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15: Eur J Pharmacol 1996 May 23;304(1-3):1-6Motor effects of lamotrigine in naive and dopamine-depleted mice.
Kaur S, Starr M
Department of Pharmacology, School of Pharmacy, London, UK.
Lamotrigine (3,5-diamino-6-[2,3-dichlorphenyl]-1,2,4-triazine) has been hypothesised to possess antiparkinsonian activity, by inhibiting the release of glutamate from basal ganglia neurones. This study therefore examined the motor effects of lamotrigine in naive and reserpine-treated mice and its interactions with dopaminergic agonists. In normal mice, lamotrigine (5-80 mg/kg i.p.) decreased spontaneous locomotor activity with high doses ( > or = 40 mg/kg) causing moderately severe impairment to posture and gait. In mice treated 24 h beforehand with reserpine (5 mg/kg i.p.), lamotrigine (5-40 mg/kg i.p.) had no effect on akinesia by itself and did not alter the locomotion induced with the selective dopamine D1 receptor agonist 2,3,4, 5-tetrahydro-7,8-dihydroxy-1-phenyl-1 H-3-benzazepine hydrochloride (SKF 38393, 30 mg/kg i.p.). By contrast, motor responses to the dopamine D2 receptor-selective agonist N-n-propyl-N-phenylethyl-p-(3-hydroxyphenyl)ethylamine (RU 24213, 5 mg/kg s.c.) and to the dopamine precursor L-3,4-dihydroxyphenylalanine (L-DOPA, 150 mg/kg i.p. in the presence of benserazide, 100 mg/kg i.p.), were significantly potentiated by 10 and 40 mg/kg i.p. lamotrigine respectively. It is suggested that lamotrigine may enhance the antiakinetic action of L-DOPA in parkinson-like mice by increasing motor responding mediated by dopamine D2 but not dopamine D1 receptors. This interaction profile of lamotrigine with dopamine D1 and D2 receptor mechanisms is opposite to what one sees with antagonists of glutamate receptors.
PMID: 8813577, UI: 96408570
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20: Life Sci 1994;54(4):245-52The novel anticonvulsant lamotrigine prevents dopamine depletion in C57 black mice in the MPTP animal model of Parkinson's disease.
Jones-Humble SA, Morgan PF, Cooper BR
Wellcome Research Laboratories, Department of Pharmacology, Research Triangle Park, NC 27709.
The effect of the novel anticonvulsant Lamotrigine (LTG) was studied on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced dopamine depletion in C57BL/6 mouse brain. Whole brain dopamine levels were measured by HPLC-ED 2 days after treatment with MPTP (15 mg/kg s.c.). While LTG alone had no direct effect on dopamine levels at two hours or two days after treatment, MPTP induced dopamine depletion was significantly less in mice pretreated with LTG (approximate ED50: 6 mg/kg). LTG (38 mg/kg) was shown to completely protect against dopamine depletion when given 1 or 2 hours prior to MPTP administration. The effect of LTG (38, 100 mg/kg) on MPTP toxicity was compared to the effects of the anticonvulsants phenytoin (67 mg/kg), carbamazepine (156 mg/kg), and riluzole (33 mg/kg) and the Ca++ channel blocker nicardipine (0.1 mg/kg). Only phenytoin and LTG showed significant protection against MPTP. Results suggest LTG prevents MPTP induced dopamine depletion via a novel mechanism.
PMID: 8289584, UI: 94118795
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