Carbamazepine has become the drug of choice in the treatment of trigeminal neuralgia. However, it can have significant side effects as well as not being effective in some cases. There is thus a very definite need for more effective and safer drugs for the treatment of this condition. Previous work in our laboratory has shown that the trigeminal nucleus of cats is a particularly useful model for investigating the mechanism of action of anticonvulsant drugs, both as regards their effect in seizure dis- orders and in trigeminal neuralgia. I therefore propose to further delineate the neuropharmacology of drugs effective against trigeminal neuralgia by investigating the neurotransmitters involved in our experimental model, and by investigating which ones of them are affected by the drugs effective, against trigeminal neuralgia. A more precise understanding of the interaction between clinically effective drugs and the neurotransmitters in our experimental model should materially add to our ability to identify the types of chemical compounds that may be useful in the treatment of trigeminal neuralgia. I will therefore first investigate the effect of the micro-iontophoretic administration of the putative neurotransmitters in the trigeminal nucleus, and of agents which alter the effects of these neurotransmitters, on the segmental inhibition and on excitatory transmission in the spinal trigeminal nucleus. Then, I will re-examine the effect of the iontophoretic administration of all these agents after the i.v. injection of the anti-trigeminal neuralgia drugs we have previously studied.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS019889-04
Application #
3399995
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
1988-03-01
Project End
1993-02-28
Budget Start
1991-03-01
Budget End
1992-02-29
Support Year
4
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of Pittsburgh
Department
Type
Schools of Medicine
DUNS #
053785812
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
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Fromm, G H; Aumentado, D; Terrence, C F (1993) A clinical and experimental investigation of the effects of tizanidine in trigeminal neuralgia. Pain 53:265-71
Fromm, G H; Sato, K; Nakata, M (1992) The action of GABAB antagonists in the trigeminal nucleus of the rat. Neuropharmacology 31:475-80
Kondo, T; Fromm, G H; Schmidt, B (1991) Comparison of gabapentin with other antiepileptic and GABAergic drugs. Epilepsy Res 8:226-31
Fromm, G H; Nakata, M; Kondo, T (1991) Differential action of amitriptyline on neurons in the trigeminal nucleus. Neurology 41:1932-6
Nakata, M; Mukawa, J; Fromm, G H (1991) Why are most GABA agonists not effective antiepileptic drugs? Jpn J Psychiatry Neurol 45:391-4
Fromm, G H; Shibuya, T; Nakata, M et al. (1990) Effects of D-baclofen and L-baclofen on the trigeminal nucleus. Neuropharmacology 29:249-54