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Tetramethylpyrazine, a drug originally isolated from the rhizome of Ligustkum walliichi, has been used routinely in China for the treatment of stroke and angina pectoris. We evaluated this drug by testing its effectiveness in increasing the survival rate in a stroke model using Mongolian gerbils. Our results indicate that tetramethylpyrazine can increase survival rate only if it is administered before the induction of cerebral ischemia. Since we administered the drug intraperitoneally, it is possible that pretreatment was necessary to increase its effective concentration in the blood. Receptor binding studies indicated that tetramethylpyrazine was inactive against a variety of pharmacologically active receptors. (Stroke 1989;20:96-99) T he rhizome of Ligusticum walliichi has long been used by practitioners of traditional Chinese medicine in treating blood stasis and vital energy stagnation. In recent years, the active ingredient of this herb has been characterized and its chemical structure has been worked out (Figure 1). This compound, tetramethylpyrazine (TMP), has been reported to be effective for the treatment of angina pectoris 1 and cerebral thrombosis 2 in China. Experimentally, TMP has been shown to induce vasodilation, to increase coronary blood flow, and to inhibit ADP-induced platelet aggregation.3 These properties of TMP apparently account for its efficacy in the treatment of disorders associated with blood vessel occlusion.Although TMP has been used in a number of clinical trials for the treatment of cerebral thrombosis in China, 2 -4 its effectiveness in increasing survival rate has not been confirmed under stringent experimental conditions. As part of our overall effort to evaluate TMP, we tested it in a stroke model using Mongolian gerbils.3 -6 The following is a report of our findings. Materials and MethodsOne hundred seventy-nine male Mongolian gerbils weighing 70-80 g were maintained in our animal house with a day/night cycle of 12/12 hours. Food and water were given ad libitum. Gerbils were stabilized for at least 1 week before the initiation of the experiment. Gerbils were anesthetized with 0.25 mg/ kg pentobarbitol in 0.5 ml injection volume before unilateral cerebral infarction was induced by ligating one common carotid artery. A segment of the artery was tied doubly, and the artery was transected between the sutures. Gerbils were returned to their cages and observed approximately every 30 minutes for 3 hours. Gerbils dying within this period were excluded from the study; <2% of the gerbils died. At the end of the third hour, gerbils were injected intraperitoneally with either 2.5 mg TMP in 0.2 ml saline or 0.2 ml saline (vehicle). Signs of ischemia were then recorded by an independent observer.We used two experimental paradigms. In the first, gerbils were pretreated with either TMP or vehicle for 7 days before the induction of stroke; in the second, gerbils were not pretreated. In both paradigms, 2.5 mg TMP or vehicle was administered intraperitoneally once daily in the morning for 4 days...

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