Calcium channel agonists and dystonia in the mouse.
Systemic administration of the L-type calcium channel agonists +/-Bay K 8644 or FPL 64176 causes a characteristic pattern of motor dysfunction in normal C57BL/6J mice that resembles generalized dystonia. There is no associated change in the electroencephalogram, confirming that the motor disorder does not reflect epileptic seizures. However, the electromyogram reveals an increase in baseline motor unit activity with prolonged phasic discharges consistent with dystonia. The duration and severity of dystonia is dependent on the dose administered and the age of the animal at testing. The effects are transient, with the return of normal motor behavior 1-4 hours after treatment. Similar effects can be provoked by intracerebral administration of small amounts of the drugs, indicating a centrally mediated response. Dystonia can be attenuated by co-administration of dihydropyridine L-type calcium channel antagonists (nifedipine, nimodipine, and nitrendipine) but not by non-dihydropyridine antagonists (diltiazem, verapamil, and flunarizine). These results implicate abnormal function of L-type calcium channels in the expression of dystonia in this model.
Jinnah
H A
HA
Department of Neurology, Johns Hopkins Hospital, Baltimore, Maryland 21287, USA.
Sepkuty
J P
JP
Ho
T
T
Yitta
S
S
Drew
T
T
Rothstein
J D
JD
Hess
E J
EJ
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D000818:Animals; D001931:Brain Mapping; D002120:Calcium Channel Agonists / Q000494:pharmacology*; D015220:Calcium Channels / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004421:Dystonia / Q000503:physiopathology*; D004569:Electroencephalography / Q000187:drug effects; D004576:Electromyography / Q000187:drug effects; D008124:Locomotion / Q000187:drug effects; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009460:Neurologic Examination / Q000187:drug effects; D011758:Pyrroles / Q000494:pharmacology*
D002120:Calcium Channel Agonists; D015220:Calcium Channels; D011758:Pyrroles; C071658:FPL 64176; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester