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Biomedical subjects

J M Hesselink

Publications and source records attributed to J M Hesselink.

10 recordsLinked to original sources
PubMed1999

Iloperidone (Hoechst Marion Roussel Inc).

Iloperidone (HP-873) is a 5-HT2 antagonist from Hoechst Marion Roussel Inc in clinical trials for the treatment of schizophrenia and psychosis. In May 1996, the company announced that it had discontinued further development of the compound. This announcement, however, was followed in January 1997 by the news that Hoechst had licensed the compound to Titan Pharmaceuticals, on a worldwide exclusive basis. Subsequently, Titan granted Novartis worldwide development, manufacturing and marketing rights, excluding Japan. In August 1998, Novartis commenced phase III trials for iloperidone to treat schizophrenia. The trial will include 3000 patients in 20 countries. In receptor binding assays it has moderate affinity for the D2 receptor and greater affinity for the 5-HT2 receptor. This is thought to be an important factor for atypical antipsychotic activity and reduction of extrapyramidal side-effects.

Journal Article↗
PubMed1995

Ipsapirone in the treatment of bulimia nervosa: an open pilot study.

Seventeen women who met the criteria for bulimia nervosa (DSM-III-R) were treated for 4 weeks in an open trial with ipsapirone, a partial 5-HT1A agonist. Bulimic symptoms diminished in 66.6% of the patients after only 1 week of treatment, 93.3% showed a reduction of more than 50% of weekly binge eating attacks after 4 weeks. The mean frequency of binges was reduced by 81% at endpoint. Ipsapirone was well tolerated.

Adult↗
PubMed1994

A phase II multicenter dose-finding, efficacy and safety trial of ipsapirone in outpatients with generalized anxiety disorder.

Benzodiazepines have been prescribed for the treatment of Generalized Anxiety Disorder (GAD) for nearly three decades due to their proven anxiolytic efficacy, despite a considerable side effect and abuse liability profile. A new class of compounds, the azapirones, have been developed as an alternative to benzodiazepine treatment. Ipsapirone is a novel anxiolytic azapirone which has high specificity for the 5-HT1A receptor and which has the potential for offering certain advantages over buspirone. The present 5-week study investigated three doses of ipsapirone (2.5mg, 5.0mg and 7.5mg tid) versus placebo in 267 GAD outpatients. Efficacy was evaluated using the Hamilton Anxiety Rating Scale (HAM-A), Zung Anxiety Scale (Zung-A), and Clinical Global Impression (CGI). The study design consisted of a 1-week placebo run-in, a 4-week double-blind treatment period, and a 1-week placebo washout. The 5.0mg group demonstrated consistently superior improvement in all efficacy variables during the treatment period, with significant differences (p < 0.05) from placebo and, at times, the 2.5mg and 7.5mg groups. Incidence of adverse events, primarily dizziness, nausea, sedation, and asthenia, was found to be dose proportional, with significant increase in the 7.5mg group, which may account for the diminished effectiveness seen with this dose. Our results suggest that ipsapirone may represent a viable treatment for GAD.

Adult↗
PubMed1993

The safety and efficacy of ipsapirone vs. lorazepam in outpatients with generalized anxiety disorder (GAD): single site findings from a multicenter trial.

We report the findings of a randomized, double-blind, placebo-controlled, parallel, generalized anxiety disorder (GAD) outpatient study. The purpose of the study was to compare the efficacy, safety, and tolerability of ipsapirone, an azapirone and 5-HT1A agonist, given at a total daily dose of 10 mg to 30 mg, with a total daily dose of 2 mg to 6 mg of lorazepam or placebo in 90 outpatients with GAD of moderate or greater severity. At baseline, all patients had a Hamilton Anxiety Scale (HAM-A) score of > or = 18 and Covi anxiety score of > or = 8. After a 1-week single-blind washout, patients entered a 4-week double-blind period with an optional extension for another 4 weeks, followed by a 2-week single-blind placebo washout. Ipsapirone and lorazepam ratings on the HAM-A and Clinical Global Impressions (CGI) were significantly (p < .05) superior to placebo at the end of the acute and maintenance periods of the trial, with a 50 percent HAM-A reduction on active drugs vs. 20 percent on placebo. The anxiety of patients receiving lorazepam, but not ipsapirone, rebounded during the final placebo washout.

Adult↗
PubMed1991

Nimodipine tested in a human model of cerebral ischaemia. Electroencephalographic and transcranial Doppler ultrasound investigations in normal subjects during standardized hyperventilation.

The anti-ischaemic properties of nimodipine 30 mg and 60 mg t.i.d. for 4 days has been tested in a double-blind, placebo-controlled, cross-over study based on the use of hyperventilation to reduce flow velocity in cerebral arteries. Whether the anti-ischaemic properties were due to a vasodilatator action on cerebral blood vessels or to an anti-ischaemic effect on cerebral neurons was studied. There was a slight cardiovascular effect, without any significant change in the EEG at rest. During standardized hyperventilation, there was no difference in the reduction in the blood flow velocity in the nimodipine and placebo groups (namely 56%, 56% and 59%). Both doses of nimodipine, however, significantly attenuated the hyperventilation-induced increase in slow EEG activity in the 1.5-6.0 Hz range. It is concluded that the anti-ischaemic properties of nimodipine are due to an effect on the central nervous system rather than to an effect on cerebral blood flow.

Adult↗
PubMedDate not supplied

The effect of nimodipine monotherapy and combined treatment with ketamine and lignocaine in aneurysmal subarachnoid haemorrhage.

The clinical effects of nimodipine monotherapy were compared with the effects of nimodipine combined with ketamine and lignocaine (combination therapy) in a single-centre, one investigator, open study in patients with proven aneurysmal subarachnoid haemorrhage (aSAH). After clipping of the aneurysm, nimodipine was administered intravenously until day 5-7 after clipping. Thereafter the intravenous nimodipine was substituted by oral doses of nimodipine. These were decreased gradually and then discontinued within the following 6 days. For combination therapy, nimodipine was given together with both a bolus injection of 1 microgram/kg ketamine followed by an infusion of the drug at a rate of 3 micrograms/kg/min and a bolus injection of 1.5 mg/kg lignocaine followed by an infusion of the drug at a rate of 12 micrograms/kg/min. During the study period, 173 patients were admitted to the hospital with subarachnoid haemorrhage (SAH). Of these patients, 115 with a proven aneurysm were operated on and evaluated: 66 patients received nimodipine monotherapy and 49 were given nimodipine combined with ketamine and lignocaine. These subgroups were comparable in terms of the baseline characteristics (age, Hunt and Hess score). The (baseline corrected) Hunt and Hess scores after surgery and a 0-5 clinical outcome score were applied as indices for clinical effects. Patients receiving nimodipine monotherapy and combined therapy showed a significant clinical improvement compared to baseline (P = 0.001 and P = 0.006, respectively). The beneficial effect of nimodipine monotherapy is in line with previous double-blind, placebo-controlled studies. Although nimodipine monotherapy seems to be more effective than combined treatment, this was not statistically significant. Our data indicate that combined treatment with ketamine and lignocaine is not more effective than nimodipine monotherapy in patients with mild aSAH, but this does not rule out an effect in severe cases. There was no indication of a pharmacodynamic interaction between nimodipine and co-medication. No serious or clinically relevant adverse reactions were noted during the study.

Adult↗