Motor effects of lamotrigine in naive and dopamine-depleted mice.
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.
Kaur
S
S
Department of Pharmacology, School of Pharmacy, London, UK.
Starr
M
M
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D000978:Antiparkinson Agents / Q000494:pharmacology; D001545:Benserazide / Q000494:pharmacology; D003864:Depression, Chemical; D004298:Dopamine / Q000502:physiology*; D018491:Dopamine Agonists / Q000494:pharmacology; D005684:Gait / Q000187:drug effects; D000077213:Lamotrigine; D007980:Levodopa / Q000494:pharmacology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects*; D010627:Phenethylamines / Q000494:pharmacology; D011187:Posture; D017447:Receptors, Dopamine D1 / Q000187:drug effects; D017448:Receptors, Dopamine D2 / Q000187:drug effects; D012110:Reserpine / Q000494:pharmacology; D014227:Triazines / Q000494:pharmacology*
D018759:Adrenergic Uptake Inhibitors; D000927:Anticonvulsants; D000978:Antiparkinson Agents; D018491:Dopamine Agonists; D010627:Phenethylamines; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D014227:Triazines; D007980:Levodopa; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; C016868:N-n-propyl-N-phenylethyl-4(3-hydroxyphenyl)ethylamine hydrochloride; D001545:Benserazide; D012110:Reserpine; D000077213:Lamotrigine; D004298:Dopamine