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Notes: For several years, osseointegrated implant-supported overdentures have been used in the rehabilitation of full edentulism with excellent results, at least in the lower jaw. This study involved 3 groups of patients with different prosthetic reconstructions:(1) mandibular overdentures supported by 2 implants connected by a bar (30 patients), (2) mandibular fixed prostheses supported by 4–6 implants (25 patients) and (3) mandibular complete dentures without implant support as controls (85 patients). The primary aim of this study was to examine on orthopantomograms (by means of the area index to minimize distortion and magnification errors), posterior mandibular ridge resorption in the 3 treatment groups. The present data demonstrated a minimal posterior mandibular ridge resorption in patients with fixed implant-supported prostheses. A more considerableposterior ridge resorption was observed in the complete denture group and especially in the overdenture wearers. For the latter, the annual posterior jaw bone resorption after the post-extraction remodeling period of 6 months, was 2- to 3-fold that of full denture wearers. When patients were edentulous for more than 10 years, the difference between the 2 latter groups disappeared. It is suggested that although the overdenture design on 2 implants offers advantages from a financial and failure rate point of view, its indications in younger patients should cautiously be evaluated in a long-term perspective concerning posterior mandibular bone resorption.

Notes: This study involved 108 patients (age 38–82 years) rehabilitated with overdentures in the lower jaw supported by 2 endosseous screw-shaped implants. At each follow-up visit, the clinical attachment level (PAL) around the implants was assessed with a Merrit-B probe or a constant force electronic probe, Peri-probe, and biannually parallel long-cone radiographs were taken to locate the marginal bone level. These data were used to examine the relationship between bone and attachment level estimations around implants. As a mean, bone level was scored 1.4 mm apically of PAL and this difference remained constant with time. The Pearson correlation coefficient between bone level and PAL, for mesial and distal sites, was 0.67 and 0.61 for the Merrit-B probe, and 0.76 and 0.65, respectively for the Peri-probe. The highest correlations were obtained for sites with a healthy gingiva or in absence of intra-bony craters. Duplicate PAL registrations showed a standard deviation for the intra-examiner variability of 0.37 (Peri-probe) or 0.40 mm (Merrit-B probe) with more than 90% of the variation within 0.5 mm. The mean difference in PAL between Merrit-B probe or Peri-probe was 0.05 mm. It was concluded that the clinical attachment level determination is a reliable indicator for bone level around implants with a moderate healthy gingiva.

Notes: Determinations of interocclusal tactile threshold levels so far have involved neither appropriate psychophysical approaches nor an assessment of the mechanical and thermal properties of the foils used. Twenty subjects (12 females) aged 18 to 50 (mean age 35) were tested for their absolute threshold level (RL). Both the method of limits and the staircase method were applied to determine the active or passive RL. For the active RL assessment, foils of different thicknesses were placed between edge-to-edge opposed incisors during gentle biting. Inner ear receptors of the blindfolded subjects were blocked by broad band noise applied through earphones, because vibrations induced by occlusal contact and conducted through bone might be perceived by these receptors. The foils presented were aluminum (Al), tin (Sn), polyester (PE) and calibrated steel (St) (thickness ranging from 8 to 50 μm) which offer different physical and thermal properties. The range of RL of the group varied between 8 μm for aluminum to 46 μm for polyester for 50% correct assessments. Increasing the foil temperature from room temperature (20°C) to body temperature (35°C) significantly increased the RL for conducting materials (one-way blocked ANOVA). These results indicate that temperature exchange takes place while presenting conducting foils at 20°C (cold stimulus) interocclusally, which influences the RL by activating thermosensitive receptors. The passive RL determination with classical von Frey-hairs resulted in a mean axial RL of 3.0 g. Both psychophysical RL assessments (method of limits, staircase method) gave reproducible and similar results as ascertained by ANOVA. Furthermore, a positive correlation was established between active and passive RL (Pearson correlation test). It is concluded that the physical and thermal properties of the foils need careful consideration in future experiments on threshold determination. Although active RL determination may involve the activation of non-periodontal receptors, it remains a realistic parameter to monitor tactile function of teeth.

Notes: Summary Levocabastine is a potent antihistamine drug, structurally unrelated to neurotensin. In rat and mouse brain but not in other animal species, it inhibited 60% of the [3H]neurotensin binding displaced by unlabelled neurotensin or neurotensin (8–13). The levocabastine-sensitive site or “site 1” displayed high affinity properties for levocabastine (IC50=25 nM) and was highly stereospecific (IC50-value higher than 10 μM for one of the isomers). Binding to the “site 1” in rat brain corresponded to the [3H]neurotensin binding displaceable by 1 μM levocabastine, whereas binding to the “site 2” corresponded to the binding displaced by 1 μM neurotensin when the “site 1” was occluded by 1 μM levocabastine. Both “site 1” and “site 2” appeared to be saturable. Scatchard plots obtained in rat bulbus olfactorius allowed to calculate a K D-values of 7.1 nM and a B max-values of 37.2 fmol/mg original tissue for “site 1”, while “site 2” displayed a K D-value of 0.7 nM and a B max-value of 16.3 fmol/mg original tissue. The regional distributions of both sites showed marked differences. The “site 1” was homogeneously distributed throughout all rat brain areas, whereas the amount of “site 2” binding was markedly different in separate brain areas: bulbus olfactorius and substantia nigra had the highest amounts (8.9 and 7.8 fmol/mg tissue) while cerebellum had the lowest (0.4 fmol/mg tissue). In spite of its high affinity and stereospecificity, “site 1” has to be considered as an acceptor or recognition site for [3H]neurotensin because of its species-link, low saturability and homogeneous distribution in all rat brain areas. On the other hand, “site 2” had the characteristics of a physiological receptor: high affinity, saturability in the low nanomolar range and marked regional distribution in rat brain. “Site 2” corresponds therefore most probably to the physiological neurotensin receptor. The foregoing experiments provide evidence for the presence of a drug displaceable, non-specific (=unrelated to a physiological receptor) neurotensin binding site in rat brain; levocabastine should be an important tool to occlude this site in order to reveal, by means of in vitro binding assays, the specific neurotensin binding site in rat brain.

Notes: Abstract This review reports on the pharmacodynamics of the new antipsychotic risperidone. The primary action of risperidone is serotonin 5-HT2 receptor blockade as shown by displacement of radioligand binding (Ki: 0.16 nM), activity on isolated tissues (EC50:0.5 nM), and antagonism of peripherally (ED50: 0.0011 mg/kg) and centrally (ED50:0.014 mg/kg) acting 5-HT2 receptor agonists in rats. Risperidone is at least as potent as the specific 5-HT2 receptor antagonist ritanserin in these tests. Risperidone is also a potent dopamine D2 receptor antagonist as indicated by displacement of radioligand binding (Ki: 1.4 nM), activity in isolated striatal slices (IC50: 0.89 nM), and antagonism of peripherally (ED50: 0.0057 mg/kg in dogs) and centrally acting D2 receptor agonists (ED50: 0.056–0.15 mg/kg in rats). Risperidone shows all effects common to D2 antagonists, including enhancement of prolactin release. However, some central effects such as catalepsy and blockade of motor activity occur at high doses only. Risperidone is 4–10 times less potent than haloperidol as a central D2 antagonist in rats and it differs from haloperidol by the following characteristics: predominant 5-HT2 antagonism; LSD antagonism; effects on sleep; smooth dose-response curves for D2 antagonism; synergism of combined 5-HT2/D2 antagonism; pronounced effects on amphetamine-induced oxygen consumption; increased social interaction; and pronounced effects on dopamine (DA) turnover. Risperidone displays similar activity at pre- and postsynaptic D2 receptors and at D2 receptors from various rat brain regions. The binding affinity for D4 and D3 receptors is 5 and 9 times weaker, respectively, than for D2 receptors; interaction with D1 receptors occurs only at very high concentrations. The pharmacological profile of risperidone includes interaction with histamine H1 and α-adrenergic receptors but the compound is devoid of significant interaction with cholinergic and a variety of other types of receptors. Risperidone has excellent oral activity, a rapid onset, and a 24-h duration of action. Its major metabolite, 9-hydroxyrisperidone, closely mimics risperidone in pharmacodynamics. Risperidone can be characterized as a potent D2 antagonist with predominant 5HT2 antagonistic activity and optimal pharmacokinetic properties.

Notes: Abstract Risperidone and its active metabolite 9-OH-risperidone were compared to reference antipsychotic drugs (haloperidol, pipamperone, fluspirilene, clozapine, zotepine) and compounds under development (olanzapine, seroquel, sertindole, ORG-5222, ziprasidone) for in vitro binding to neurotransmitter receptors in brain tissue and on membranes of recombinant cells expressing cloned human receptors and for in vivo occupancy of neurotransmitter receptors in rat and guinea-pig brain following acute treatment (2 h., s.c.). An ex vivo autoradiography technique was applied to determine the receptor occupancy by the drugs administered in vivo. Of particular interest are the central 5HT2A receptors and D2-type receptors. Predominant 5HT2A receptor antagonism is supposed to add to an atypical profile of the antipsychotics (treatment of the negative symptoms, low incidence of extrapyramidal side effects). D2 antagonism is required for the treatment of positive symptoms. A contribution of the new dopamine receptor subtypes D3 and in particular D4 receptors has been proposed. In vitro, all compounds, except the ‘typical’ antipsychotics haloperidol and fluspirilene, showed higher affinity for 5HT2A than for D2 receptors. Subnanomolar affinity for human 5HT2A receptors was observed for ORG-5222, sertindole, resperidone, 9-OH-risperidone and ziprasidone. Fluspirilene, ORG-5222, haloperidol, ziprasidone, risperidone, 9-OH-risperidone and zotepine displayed nanomolar affinity for human D2 receptors. Sertindole and olanzapine were slightly less potent. Pipamperone, clozapine and seroquel showed 2 orders of magnitude lower D2 affinity in vitro. Clozapine, but even more so pipamperone, displayed higher affinity for D4 than for D2 receptors. For most other compounds, D4 affinity was only slightly lower than their D2 affinity. Seroquel was totally devoid of D4 affinity. None of the compounds had nanomolar affinity for D1 receptors; their affinity for D3 receptors was usually slightly lower than for D2 receptors. In vivo, ORG-5222, risperidone, pipamperone, 9-OH-risperidone, sertindole, olanzapine, zotepine and clozapine maintained a higher potency for occupying 5HT2A than D2 receptors. Risperidone and ORG-5222 had 5HT2A versus D2 potency ratio of about 20. Highest potency for 5HT2A receptor occupancy was observed for ORG-5222 followed by risperidone and olanzapine. Ziprasidone exclusively occupied 5HT2A receptors. ORG-5222, haloperidol, fluspirilene and olanzapine showed the highest potency for occupying D2 receptors. No regional selectivity for D2 receptor occupancy in mesolimbic versus nigrostriatal areas was detected for any of the test compounds. Risperidone was conspicuous because of its more gradual occupancy of D2 receptors; none of the other compounds showed this property. The various compounds also displayed high to moderate occupancy of adrenergic α1 receptors, except fluspirilene and ziprasidone. Clozapine, zotepine, ORG-5222 and sertindole occupied even more α1 than D2 receptors. Clozapine showed predominant occupancy of H1 receptors and occupied cholinergic receptors with equivalent potency to D2 receptors. A stronger predominance of 5HT2A versus D2 receptor occupancy combined with a more gradual occupancy of D2 receptors differentiates risperidone and its 9-OH-metabolite from the other antipsychotic compounds in this study. The predominant 5HT2A receptor occupancy probably plays a role in the beneficial action of risperidone on the negative symptoms of schizophrenia, whereas maintenance of a moderate occupancy of D2 receptors seems adequate for treating the positive symptoms of schizophrenia. A combined 5HT2A and D2 occupancy and the avoidance of D2 receptor overblockade are believed to reduce the risk for extrapyramidal symptoms.