Tiagabine anticonvulsant

In parallel with the identification of distinct transporters for GABA there has been continued interest in the development of selective blockers of these transporters and the therapeutic potential that could result from prolonging the action of synaptically released GABA. It has been known for a long time that certain pro-drugs of nipecotic add (e.g. nipecotic acid ethyl ester) are able to cross the blood-brain barrier and are effective anticonvulsants in experimental models of epilepsy. More recently, several different systemically active lipophillic compounds have been described that act selectively on GAT-1, GAT-2 or GAT-3 (Fig. 11.4). Of these, tiagabine (gabitiil), a derivative of nipecotic acid that acts preferentially on GAT -1, has proved clinically useful in cases of refractory epilepsy. 

Anticonvulsants. Several antiseizure medicines have been studied in the treatment of PTSD, and some results have been encouraging. Open label studies, first with carbamazepine (800-1200 mg/day) and later with valproate (500-2000 mg/ day), demonstrated overall improvement in PTSD patients, though not for intrusive recollections per se. Recent open label studies of gabapentin, lamotrigine, tiagabine, and topiramate have suggested these anticonvulsants might also be helpful for some PTSD symptoms. 

Thioridazine (Mellaril) Antipsychotic Thiothixene (Navane) Antipsychotic Tiagabine (Gabatril) Anticonvulsant... 

Tiagabine is an anti-convulsive medication also used in the treatment for panic disorder as are a few other anticonvulsants. It does appear to operate as a selective GABA reuptake inhibitor. Tiagabine s most common side effects include confusion, difficulty speaking clearly/stuttering and mild sedation. 

Other agents with anticonvulsant properties that may be of use m the treatment of bipolar disorder include topiramate, gabapentin, tiagabine and carbamazepine (Janicak et al., 2001). 

Tiagabine is another recently approved anticonvulsant whose mechanism of action is thought to be blockade of GABA reuptake. Preliminary experience in an open-label trial of either monotherapy or augmentation therapy with this agent has not been promising ( 241). 

The newer anticonvulsants have not been studied as intensively as the older drugs as regards the possibility of interference with the effects of oral contraceptives. The available data suggest that women taking oral contraceptives can also take gabapentin, lamotrigine, tiagabine, and... 

Gabapentin, tiagabine, other anticonvulsants, even opiates if done by experts while monitoring carefully in difficulf cases (for chronic pain)... 

For neuropathic pain, tricyclic antidepressants and SNRIs as well as tiagabine, other anticonvulsants, and even opiates can augment pregabalin if done by experts while carefully monitoring in difficult cases... 

Stahl SM. Anticonvulsants as anxiolytics, part f tiagabine and other anticonvulsants with actions on GABA. J Clin Psychiatry. 2004 65 29f-2. 

Of the newer anticonvulsants, lamotrigine, gabapentin, tiagabine, and vigabatrin have little or no teratogenic potential in animals, whereas oxcarbazepine and topira-mate are teratogenic in rodents. However, animal studies are not necessarily apphcable to humans and chnical data are stiU insufficient to assess the effects of newer drugs on the development of the human fetus (153). 

The most important interactions of tiagabine involve induction of its metabolism by enzyme-inducing anticonvulsants (30). This results in larger tiagabine dosage requirements compared with patients taking monotherapy or valproic acid co-medication. 

Nousiainen I, Mantyjaryi M, Kalviainen R. Visual function in patients treated with the GABAergic anticonvulsant drug tiagabine. Clin Drug Invest 2000 20 393-400. 

A review of the second-generation anticonvulsants reveals that screening or serendipity led to the development of felbamate (10), 1am-otrigine (11), zonisamide (13), topiramate (15), and levetiracetam (16) on the other hand, clobazam (4d) and oxcarbazepine (12) were developed by structural variation of known agents (78). Only three, vigabatrin (8), gabapentin (9), and tiagabine (14), were developed by mechanism-based rational development (78). 

The place in therapy of the newer anticonvulsants, such as gabapentin, levetiracetam, tiagabine, topiramate, and zon-isamide, is controversial. Many clinicians consider these agents to be less effective than established mood stabilizers based on initial studies and avoid them for monotherapy in bipolar disorder. 

Table IV-1 -3 summarizes the mechanisms, indications for use, and potential toxic effects of some i newer anticonvulsants. Those listed are felbamate, gabapentin, lamotrigine, tiagabine, topiramate, and j...

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