Pharmacokinetics of repinotan in healthy and brain injured animals

  title={Pharmacokinetics of repinotan in healthy and brain injured animals},
  author={Thomas Schwarz and Bernhard Beckermann and Klaus Buehner and Frank Mauler and Joachim Schuhmacher and Dietrich Seidel and Wolfram Steinke and Corinna Weinz and Dieter Zimmerd},
  journal={Biopharmaceutics \& Drug Disposition},
Repinotan hydrochloride (repinotan) is a highly potent and selective 5‐HT1A full receptor agonist. The ability of repinotan to cross the blood–brain barrier (BBB) and penetrate into rat brain tissue was investigated, because rapid penetration into brain tissue is thought to be essential for neuroprotective efficacy. Intravenous (i.v.) repinotan was rapidly distributed into brain, and the distribution equilibrium between blood and brain was reached immediately after the start of infusion. Free… 
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.
Repinotan, a Selective 5-HT1A-R-Agonist, Antagonizes Morphine-Induced Ventilatory Depression in Anesthetized Rats
The 5-HT1A-R-agonist repinotan activates spontaneous breathing in anesthetized rats even in morphine-induced ventilatory depression, and the interaction with the standard opiate morphine is established.
Selective 5-HT1A-R-agonist Repinotan Prevents Remifentanil-induced Ventilatory Depression and Prolongs Antinociception
Repinotan prevented remifentanil-induced ventilatory depression in spontaneously breathing, anesthetized rats and prolonged the profound antinociception after discontinuation of remifENTanil infusion.
The role of the serotonin receptor subtypes 5-HT1A and 5-HT7 and its interaction in emotional learning and memory
Findings highlight the differential role of these 5-HTRs in cognitive/emotional domains of behavior and indicate that tonic and phasic 5-HT release can exert different and potentially opposing effects on emotional memory, depending on the states of5-HT1ARs and 5- HT7Rs and their interaction.


Neuroprotective Efficacy of Repinotan HCl, a 5-HT1A Receptor Agonist, in Animal Models of Stroke and Traumatic Brain Injury
  • F. Mauler, E. Horváth
  • Medicine
    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 neuroprotective effect of a new serotonin receptor agonist, BAY X3702, upon focal ischemic brain damage caused by acute subdural hematoma in the rat
The result indicates that this novel, high affinity 5-HT(1A) agonist, BAY X3702, is neuroprotective in this model of acute subdural hematoma and significantly smaller compared to the vehicle-treated ASDH group.
The biphasic opening of the blood-brain barrier to proteins following temporary middle cerebral artery occlusion
The behavior of the blood-brain barrier (BBB) was studied in cats following release after 1-h middle cerebral artery (MCA) occlusion and no EB extravasations were observed at any time in cats in which the rCBF during Occlusion was above 15 ml/100 g/min and which failed to show a marked reactive hyperemia.
Neuroprotective effect of 5-HT1A receptor agonist, Bay X 3702, demonstrated in vitro and in vivo.
It is found that Bay X 3702, a highly potent and selective 5-HT1A receptor agonist, has a neuroprotective potency associated with its ability to inhibit ischemia-induced excessive release of glutamate, and might be useful for the treatment of acute cerebral infarction.
Inhibition of evoked glutamate release by the neuroprotective 5-HT1A receptor agonist BAY x 3702 in vitro and in vivo
In rat hippocampal slices BAY x 3702 inhibited evoked glutamate release in a dose-dependent manner and was blocked by the selective 5-HT(1A) receptor antagonist WAY 100635, indicating that BAYx 3702 specifically acts via 5- HT( 1A) receptors.
Blood-brain barrier disruption in experimental focal ischemia: comparison between in vivo MRI and immunocytochemistry.
A rabbit model of focal cerebral ischemia is used to compare GdDTPA-enhanced MRI with spin-echo images of brain injury and immunocytochemical detection of BBB damage and vasogenic edema and it appeared that large and more severe lesions corresponded to peripheral enhancement whereas smaller lesions showed central parenchymal enhancement.
In vivo actions of the selective 5-HT1A receptor agonist BAY x 3702 on serotonergic cell firing and release
Results indicate that the systemic administration of BAY x 3702 reduces the 5-HT release with high potency through the activation of midbrain 5- HT1A receptors.
Synthesis of [14C]-labelled repinotan hydrochloride and its major metabolite M-6
For studies of pharmacokinetics and drug metabolism of the new 5-HT1A agonist repinotan, the 14C-labelled version was synthesized. Starting from [U-14C]phenol, a 10-step synthesis led to 457 mg (1.58
Preclinical toxicological testing and safeguards in clinical trials
The aims of preclinical toxicology in drug development are those of understanding the pharmacology of the compound sufficiently to make the judgement that it is safe to go into a clinical trial for a stated clinical protocol (defining types of patient, numbers of patients, dose and number of doses, and intensity of monitoring).
Transport of small molecules through the blood-brain barrier: biology and methodology
Abstract The development of small molecules as effective neuropharmaceuticals requires that these compounds undergo significant transport through the brain capillary endothelial wall, which makes up