Allosteric Modulators for mGlu Receptors

The metabotropic glutamate receptor family comprises eight subtypes (mGlu1-8) of G-protein coupled receptors. mGlu receptors have a large extracellular domain which acts as recognition domain for the natural agonist glutamate. In contrast to the ionotropic glutamate receptors which mediate the fast excitatory neurotransmission, mGlu receptors have been shown to play a more modulatory role and have been proposed as alternative targets for pharmacological interventions. The potential use of mGluRs as drug targets for various nervous system pathologies such as anxiety, depression, schizophrenia, pain or Parkinson’s disease has triggered an intense search for subtype selective modulators and resulted in the identification of numerous novel pharmacological agents capable to modulate the receptor activity through an interaction at an allosteric site located in the transmembrane domain. The present review presents the most recent developments in the identification and the characterization of allosteric modulators for the mGlu receptors

A Rare Complication of a Vaginal Breech Delivery

Rectal lesions without anal sphincter trauma in childbirth are only sporadically described in literature. We describe the case of a 29-year-old primigravida who delivered a child in frank breech presentation. During the second stage of labour a foot presented transanally through a rectal laceration with intact anal sphincters. The laceration was repaired immediately after delivery in theatre. Follow-up visits showed a properly cured laceration and no complaints of incontinence or foul discharge

Apomorphine-induced disruption of prepulse inhibition that can be normalised by systemic haloperidol is insensitive to clozapine pretreatment

Rationale: Prepulse inhibition (PPI) of startle refers to the phenomenon in which a weak prepulse attenuates the startle response to a succeeding intense stimulus. PPI can be disrupted by systemic apomorphine in animals, and reduced PPI has been consistently reported in schizophrenia patients. The ability of the atypical antipsychotic clozapine to reverse apomorphine-induced PPI deficit has been demonstrated in the rat, but has not yet been tested in the mouse. The present study was designed to fill this gap. Objective and results: We investigated the efficacy of clozapine in reversing apomorphine-induced (2.0 or 2.5mg/kg, SC) PPI deficit in C57BL6 mice. Clozapine failed to restore PPI disruption in apomorphine-treated mice in two independent laboratories across two dose ranges (1-3mg/kg, IP, or 3-30mg/kg, PO), whereas the typical antipsychotic haloperidol (1mg/kg,IP) completely normalised PPI performance. Conclusions: Unlike the rat, apomorphine-induced PPI disruption in mice might be instrumental in distinguishing between typical and atypical antipsychotic drugs. This also lends further support to the suggestion that the neuropharmacology of PPI is not identical in the two rodent specie