Systemic and cerebral hemodynamic responses to the noncompetitive N-methyl-D-aspartate (NMDA) antagonist CNS 1102.

Published

Journal Article

The excitatory amino acid antagonists are being developed as neuroprotective drugs aimed at limiting ischemic neuronal damage. Their hemodynamic and neurologic side effects are important in assessing safety and tolerability. We studied CNS 1102, a high-affinity noncompetitive N-methyl-D-aspartate (NMDA) receptor-channel antagonist, in normal volunteers. The effects of 2 mg CNS 1102 were assessed in a single-blind, placebo-controlled, fixed-dose, cross-over trial comparing administration by intravenous infusion for 15 min or bolus for 2 min in 8 healthy male subjects. Cerebral hemodynamics were studied with carotid and vertebral duplex ultrasound imaging, common carotid artery walltracking, and middle cerebral artery velocity readings. CNS 1102 administration was associated with light-headedness, mild disorientation, perioral and peripheral paresthesias, and flushing. Mean arterial blood pressure (MAP) increased significantly from baseline 1 h after CNS 1102 administration, with a maximal increase of 17 mm Hg over placebo. Pulse rate was unchanged. Common carotid artery pulsatility decreased by 38.4% [8.3-64.5, 95% confidence interval (CI)] and vertebral pulsatility by 43.8% [11.5-74.1], both p < 0.02. No significant differences were detected for other velocity and flow parameters. Middle cerebral artery mean velocity increased by 4.6 cm/s (1.6-7.8 cm/s) and diastolic velocity by 4.6 cm/s (2.4-7.3 cm/s) (both p < 0.01), but systolic velocity was unchanged. The middle cerebral pulsatility index decreased by 11% (3.8-16.1), p < 0.001. CNS 1102 is well tolerated at a fixed dose of 2 mg in normal volunteers. Cerebral arteriolar constriction is inferred from the ultrasound results.(ABSTRACT TRUNCATED AT 250 WORDS)

Full Text

Cited Authors

  • Grosset, DG; Muir, KW; Lees, KR

Published Date

  • May 1995

Published In

Volume / Issue

  • 25 / 5

Start / End Page

  • 705 - 709

PubMed ID

  • 7630148

Pubmed Central ID

  • 7630148

Electronic International Standard Serial Number (EISSN)

  • 1533-4023

International Standard Serial Number (ISSN)

  • 0160-2446

Digital Object Identifier (DOI)

  • 10.1097/00005344-199505000-00004

Language

  • eng