Glycoprotein IIb/IIIa inhibitors in acute ST segment elevation myocardial infarction.

Limitations in the standard treatment of acute myocardial infarction have focused attention on inhibition of platelet activity by its final common pathway of activation, the glycoprotein IIb/IIIa receptor. Animal studies have suggested that a glycoprotein IIb/IIIa inhibitor could accelerate thrombolysis and prevent reocclusion after successful thrombolysis. Studies evaluating the use of a glycoprotein IIb/IIIa inhibitor alone without thrombolysis or percutaneous transluminal coronary revascularization do not suggest that isolated use of glycoprotein IIb/IIIa inhibitors restores TIMI 3 flow in a sufficient proportion of patients. Clinical studies evaluating the combination of thrombolytic therapy and glycoprotein IIb/IIIa inhibitors appear most promising, with evidence of improved angiographic outcomes. Reducing the dose of thrombolytic agents may result in reduction in bleeding risk. Current and future trials will investigate reduced-dose reteplase with abciximab and eptifibatide with reduced-dose alteplase. Available evidence suggests that glycoprotein IIb/IIIa inhibition may facilitate thrombolysis, thus adding a new element to future reperfusion regimens.

Delta antagonist and kappa agonist activity of Naltriben: evidence for differential kappa interaction with the delta 1 and delta 2 opioid receptor subtypes.

The selective delta 2 receptor antagonist Naltriben (NTB) has played an important role in the identification of subtypes of the delta opioid receptor, termed delta 1 and delta 2, and their role in antinociception. However, the majority of these studies have been conducted in the mouse. The present study determined the opioid receptor selectivity of subcutaneously (s.c.) administered NTB in the rat. Five minute pretreatment with 1 mg/kg s.c. NTB antagonized the increase in TFL produced by i.t. administration of equieffective doses of the delta 2 receptor agonist [D-Ala2,Glu4]deltorphin (DELT) or the delta 1 receptor agonist [D-Pen2, D-Pen5]enkephalin (DPDPE), but did not antagonize the mu receptor agonist [D-Ala2, MePhe4, Gly-ol5]enkephalin (DAMGO). These data confirm previous reports that NTB is a selective delta opioid receptor antagonist. However, this dose of NTB antagonized DELT and DPDPE to an equivalent extent, suggesting that its selectivity for the delta 2 receptor is not maintained after s.c. administration in the rat. A lower dose of NTB (0.56 mg/kg s.c.) was ineffective. When the dose of NTB was increased to 3 mg/kg s.c. the antagonism of DELT and of DPDPE was unexpectedly lost. Pretreatment with the kappa receptor antagonist norbinaltorphimine (nor-BNI) partially restored the antagonism of DELT, but not DPDPE by this dose of NTB and did not modify the antagonism of DAMGO by NTB. These data suggest that high doses of NTB have kappa receptor agonist-like activity and support the proposal that kappa opioid agonists diminish the actions of delta receptor antagonists. They also suggest that nor-BNI-sensitive kappa opioid receptors interact with delta 2, but not delta 1 opioid receptors in the spinal cord.