The neuroprotective effect of a new serotonin receptor agonist, BAY X3702, upon focal ischemic brain damage caused by acute subdural hematoma in the rat

  title={The neuroprotective effect of a new serotonin receptor agonist, BAY X3702, upon focal ischemic brain damage caused by acute subdural hematoma in the rat},
  author={Beat Alessandri and Eiji Tsuchida and Ross M. Bullock},
  journal={Brain Research},

A review of the neuroprotective properties of the 5-HT1A receptor agonist repinotan HCl (BAYx3702) in ischemic stroke.

The dose- and time-dependent neuroprotective efficacy of repinotan indicates that the drug is a promising candidate for prevention of secondary brain damage in brain-injured patients suffering from acute ischemic stroke, however, the first, randomized, double blind, placebo-controlled clinical trial did not demonstrate the efficacy of the drug.

Neuroprotective Efficacy of Repinotan HCl, a 5-HT1A Receptor Agonist, in Animal Models of Stroke and Traumatic Brain Injury

  • F. MaulerE. Horváth
  • Medicine, Biology
    Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
  • 2005
The favorable neuroprotective efficacy, broad dose–response curve, and prolonged therapeutic window observed in all models strongly suggest that repinotan is a promising candidate for treating acute ischemic stroke in humans.

The therapeutic efficacy conferred by the 5-HT(1A) receptor agonist 8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) after experimental traumatic brain injury is not mediated by concomitant hypothermia.

It is confirmed that a single systemic administration of 8-OH-DPAT confers neurological protection after TBI, and it is demonstrated that the beneficial effect is not mediated by concomitant hypothermia.

Traumatic brain injury-induced cognitive and histological deficits are attenuated by delayed and chronic treatment with the 5-HT1A-receptor agonist buspirone.

Data indicate that BUS has a narrow therapeutic dose response, and that 0.3 mg/kg is optimal for enhancing spatial learning and memory in this model of TBI.

Agonists at the serotonin receptor (5-HT(1A)) protect the retina from severe photo-oxidative stress.

5-HT(1A) agonists provided potent and complete functional and structural protection and AL-8309B is under evaluation in the clinic and may be useful in treating age-related macular degeneration.

5-HT1a activation in PO/AH area induces therapeutic hypothermia in a rat model of intracerebral hemorrhage

The findings suggest that chemical hypothermia targeting 5-HT1a receptor in PO/AH area could act as a novel therapeutic manner against ICH, which may provide a breakthrough for therapeutic Hypothermia.



The neuroprotective effect of the forebrain-selective NMDA antagonist CP101,606 upon focal ischemic brain damage caused by acute subdural hematoma in the rat.

A new forebrain-selective polyamine site NMDA antagonist is evaluated in a rat subdural hematoma (SDH) model and has shown a magnitude of neuroprotection which is comparable with that seen with "first-generation" NMDA antagonists such as MK801, D-CPP-ene and CGS19755.

Focal ischemic damage is reduced by CPP-ene studies in two animal models.

It is indicated that competitive N-methyl-D-aspartate antagonists may be clinically useful after traumatic intracranial hematomas and neuroprotective efficacy in a gyrencephalic species comparable to that of noncompetitive antagonists thus can be achieved with this agent.

Ischemic neuronal damage after acute subdural hematoma in the rat: effects of pretreatment with a glutamate antagonist.

The anti-ischemic efficacy of NMDA antagonists in an animal model of intracranial hemorrhage is demonstrated and excitotoxic mechanisms (which are susceptible to antagonism by D-CPP-ene) may play a role in the ischemic brain damage observed in patients who die after acute subdural hematoma.

Effects of 5‐Hydroxytryptamine1A‐Receptor Agonists on Hippocampal Damage After Transient Forebrain Ischemia in the Mongolian Gerbil

Testing the full agonists Bay R 1531 and 8-OH-DPAT and the partial agonists ipsapirone and gepirone in the model of transient global ischemia in the Mongolian gerbil suggests that transient forebrain ischemian may not be the optimal model system to demonstrate clearly the neuroprotective activity of 5-HT1A-receptor agonists.

The effect of the glycine site-specific N-methyl-D-aspartate antagonist ACEA1021 on ischemic brain damage caused by acute subdural hematoma in the rat.

Both pre- and posttreatment with ACEA1021 significantly reduced hemispheric ischemic damage produced by SDH, and the robust posttreatment effect implies that human studies with this compound should be performed in head injured patients, subject to completion of toxicology testing.

Neuroprotection by dextromethorphan in acute experimental subdural hematoma in the rat.

Because of its safety in humans and efficacy as a neuroprotectant in a variety of models, dextromethorphan may be a promising agent for clinical use, particularly in children.

Effect of neuroprotective N-methyl-D-aspartate antagonists on increased intracranial pressure: studies in the rat acute subdural hematoma model.

The three glutamate antagonists did not significantly affect ICP or cerebral perfusion pressure, but they were associated with a significantly smaller zone of focal brain damage, when compared to the mannitol and saline groups.

Effect of the novel high-affinity glycine-site N-methyl-D-aspartate antagonist ACEA-1021 on 125I-MK-801 binding after subdural hematoma in the rat: an in vivo autoradiographic study.

In vivo autoradiography studies show intense foci of penumbral NMDA receptor-mediated ion channel activation after onset of SDH, which is markedly reduced by an NMDA antagonist.

A use-dependent sodium channel antagonist, 619C89, in reduction of ischemic brain damage and glutamate release after acute subdural hematoma in the rat.

Results show that 619C89 is highly neuroprotective in this model and that its effects may, in part, be mediated by the inhibition of glutamate release from the ischemic cortex underneath the hematoma.