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. 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 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.

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 and the carbon-14 labelled major metabolite, hydroxylated in the 6-position of the chromane moiety, was synthesised as reference compound.

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).