Methyllycaconitine fails to inhibit electrically precipitated tonic hindlimb extension in mice.
Abnormalities of the transduction of the acetylcholine signal in the brain by the alpha(7) nicotinic receptor are thought to contribute substantially to a fundamental pathophysiologic mechanism in schizophrenia. Abnormal or diminished expression of the alpha(7) nicotinic receptor polypeptide subunit in the brains of patients with schizophrenia has encouraged consideration of the development of alpha(7) nicotinic receptor agonist strategies for the treatment of this disorder. These strategies would target negative symptoms, and attentional and cognitive abnormalities, which are domains of psychopathology that are associated with very poor functional outcomes and disability. Unfortunately, a major theoretic limitation to the development of alpha(7) nicotinic receptor agonist interventions for the pharmacotherapy of schizophrenia is the development of seizures. In the current study, intraperitoneally administered methyllycaconitine, a selective alpha(7) nicotinic receptor antagonist, was shown to be unable to antagonize electrically precipitated seizures in mice. These data suggest that the alpha(7) nicotinic receptor does not mediate this type of seizure activity in mice. Also, although the medication-induced emergence of seizure activity remains a real concern with the development of alpha(7) nicotinic receptor agonist strategies, the data suggest that there should be lessened concern about precipitating seizures related to electrically precipitated tonic hindlimb extension in mice.
Deutsch
Stephen I
SI
Mental Health Service Line, Veterans Integrated Service Network, Linthicum, Maryland, USA. Stephen.Deutsch@med.va.gov
Rosse
Richard B
RB
Bellack
Alan S
AS
Billingslea
Eddie N
EN
Mastropaolo
John
J
D000157:Aconitine / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004597:Electroshock / Q000379:methods*; D004830:Epilepsy, Tonic-Clonic / Q000503:physiopathology* / Q000517:prevention & control; D006614:Hindlimb; D008297:Male; D051379:Mice
C054634:methyllycaconitine; D000157:Aconitine