0.05～0.2?l of HRP (Sigma Ⅵ) were introduced into the periaqueduetal gray (PAG) of 45 rats at the superior collicular level, each brain was sectioned and processed with DAB, BDHC, O-D and TMB reactions. 29 were chosen for analysis and according to the locations of the injection center and the extent of reaction, were divided into 3 groups:1. The injection center was found in the lateral part of PAG; the reaction only involved a small area within PAG (11 rats), labeled cells were seen in PAG, tectum, reticular formation (RF) and dorsal raphe nucleus.2. The injection center was in the dorsolateral part of PAG; the reaction area extended out of PAG to the nearby RF and tectum (9 rats); labeled cells were seen in the structures mentioned in group 1 as well as in habenular nucleus (hn), parafascicular nucleus (PFN), hypothalamic nuclei (anterior, posterior, ventromedial, dorsomedial, lateral), thalamic nuclei (lateral, reticular, medial part of ventral nucleus), paraventricular gray (PVG), nucleus of the optic tract, nucleus of posterior commissure (NPC), parabigeminal nucleus (PBN), locus ceruleus, ventral nucleus of lateral geniculate body, entopeduncular nucleus.3. The injection center was in the lateral or ventrolateral part of PAG, the reaction area extended to the nearby RF, tegmentum and part of tectum (9 rats), labeled cells were seen in the structures mentioned in group 1 as well as in substantia nigra, H_1, H_2, zona inserta, HN, PFN, PVG, NPC, PBN, locus ceruleus, pretectral area and nuclei of hypothalamus. In this group 3 rats were processed with TMB reaction. Labeled cells were seen not only in the above-mentioned structures but also in the deep layers of anterior cingulate cortex (areas 23 and 24), nucleus raphe magnus, nucleus reticularis gigantocellularis, periventricular gray of 4th ventricle, dentate nucleus of cerebellum, lamina Ⅴ～Ⅶ of cervical spinal cord (the other segments were left out), preoptic and supraoptic nuclei, suprachiasmatic nucleus, anterior nucleus of mammillary body, medial nucleus of amygdaloid nucleus, spinal nucleus of nerve Ⅴ. The labelled cells were seen chiefly in the ipsilateral side. Neuronal connections also were analysed according to the disparity in labelled structures.

Batifiban, a synthetic cyclic peptide, is a potent platelet glycoprotein GPIIb/IIIa antagonist which may be useful in the treatment and prevention of acute coronary syndromes. The pharmacokinetics and pharmacodymanic (inhibition of platelet aggregation) effects, and tolerability of batifiban were investigated in healthy subjects following single bolus injection with doses of 55, 110, or 220 microg/kg, or multiple doses of an bolus followed intravenous infusion for 24 h (180 microg/kg plus 2.0 microg/min.kg, and 220 microg/kg plus 2.5 microg/min.kg) in this phase I clinical trial. Plasma levels of batifiban and areas under the curve were found to be proportional to doses. Batifiban was rapidly eliminated with a half-life of approximately 2.5 h. Significant differences were noted for plasma levels of batifiban and areas under the curve between males and females. No significant differences in the terminal half-life were found between males and females. Batifiban reversibly inhibited ex vivo platelet aggregation in a dose- and concentration-dependent manner, consistent with its mechanism as a GPIIb/IIIa antagonist. Single and multiple intravenous doses of batifiban were found to be safe and well tolerated in healthy subjects. These results support a bolus injection plus intravenous infusion regimen of batifiban for the treatment and prevention of acute coronary syndromes.
Injections, Intravenous ; Peptides, Cyclic/*pharmacokinetics ; Peptides, Cyclic/*pharmacology ; Platelet Aggregation Inhibitors/adverse effects ; Platelet Aggregation Inhibitors/*pharmacokinetics ; Platelet Aggregation Inhibitors/*pharmacology ; Platelet Glycoprotein GPIIb-IIIa Complex/*antagonists & inhibitors ; Young Adult

Batifiban,a synthetic cyclic peptide,is a potent platelet glycoprotein GPⅡb/Ⅲa an-tagonist which may be useful in the treatment and prevention of acute coronary syndromes. The pharmacokinetics and pharmacodymanic (inhibition of platelet aggregation) effects,and tolerability of batifiban were investigated in healthy subjects following single bolus injection with doses of 55,110,or 220 μg/kg,or multiple doses of an bolus followed intravenous infusion for 24 h (180 μg/kg of batifiban and areas under the curve were found to be proportional to doses. Batifiban was rapidly eliminated with a half-life of approximately 2.5 h. Significant differences were noted for plasma lev-els of batifiban and areas under the curve between males and females. No significant differences in the terminal half-life were found between males and females. Batifiban reversibly inhibited ex vivo platelet aggregation in a dose- and concentration-dependent manner,consistent with its mechanism as a GP Ⅱb/Ⅲa antagonist. Single and multiple intravenous doses of batifiban were found to be safe and well tolerated in healthy subjects. These results support a bolus injection plus intravenous infusion regimen of batifiban for the treatment and prevention of acute coronary syndromes.