piperidines and metylperon

In vitro animal studies suggest melperone, a neuroleptic butyrophenone, to be a type III antiarrhythmic drug according to the classification of Vaughan Williams. It has no negative inotropic effect on cardiac muscle. A double-blind trial of 3 hours' duration was carried out with melperone and placebo in 26 patients admitted to the CCU with suspected acute myocardial infarction (AMI) and ventricular arrhythmias. Melperone, 50 mg i.v., was superior to placebo in reducing the total number of ventricular ectopic beats (VEB) as well as the number of minutes with either frequent, multifocal, R-on-T-type or runs of VEB. The reduction became statistically significant in the second treatment hour in patients with definite AMI. Melperone induced sedation and reduction of systemic BP in most of the patients. Two patients with low initial systolic BP achieved a further reduction and had BP levels below 90 mmHg. Two patients experienced minor side-effects. In conclusion, melperone administered in large i.v. doses to patients with AMI induced sedation, acute BP reduction and some reduction of ventricular arrhythmia. X

Topics: Aged; Arrhythmias, Cardiac; Blood Pressure; Butyrophenones; Double-Blind Method; Female; Heart Rate; Heart Ventricles; Humans; Male; Middle Aged; Myocardial Infarction; Piperidines; Placebos

In a double-blind study in chronic alcoholics melperone (Buronil) was shown to significantly improve muscular and nervous tension, emotional lability, somatization, ability to sleep, anxiety, depression, paranoid ideation and presumed ability to work, but had no effect on alcoholic craving. The results received from three rating scales, and the theoretical aspects of alcoholism are discussed.

Topics: Adult; Alcoholism; Antipsychotic Agents; Butyrophenones; Clinical Trials as Topic; Double-Blind Method; Humans; Middle Aged; Piperidines; Placebos; Psychiatric Status Rating Scales; Surveys and Questionnaires

Topics: Adolescent; Adult; Aggression; Antipsychotic Agents; Butyrophenones; Clinical Trials as Topic; Double-Blind Method; Drug Evaluation; Female; Humans; Intellectual Disability; Piperidines; Self Mutilation

In a 2-wk randomized double blind study 60 chronic alcoholics were treated with either melperone (Buronil) or placebo. The patients were assessed daily using a scale including 4 items: tension, depression, craving and sleep. Statistically significant improvement was achieved in the placebo group only for "tension" and "sleep"; whereas, in the melperone group all four items improved significantly. Comparison between the groups revealed statistically significant superiority of melperone over placebo for the item "craving".

Topics: Adult; Alcoholism; Butyrophenones; Clinical Trials as Topic; Depression; Double-Blind Method; Humans; Male; Middle Aged; Piperidines; Placebos; Sleep; Surveys and Questionnaires

Topics: Adult; Butyrophenones; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Middle Aged; Piperidines; Prolactin; Receptors, Dopamine; Schizophrenia; Substance Withdrawal Syndrome; Thiothixene; Tranquilizing Agents

Topics: Adult; Aged; Blood Pressure; Butyrophenones; Chlorpromazine; Clinical Trials as Topic; Depression, Chemical; Female; Humans; Hypotension, Orthostatic; Male; Middle Aged; Piperidines; Placebos; Posture; Vertigo

Clozapine (CLZ), an atypical antipsychotic drug (APD), produces minimal extrapyramidal side effects (EPS) and has significant advantages for treating both positive and negative symptoms in schizophrenic patients. CLZ has been established as a discriminative cue in the drug discrimination paradigm and in generalization tests the CLZ cue is more selective for atypical, rather than typical, APDs. However, greater selectivity for atypical antipsychotics has been demonstrated with a lower (1.25 mg/kg) CLZ training dose in rats [Psychopharmacology, 149 (2000) 189], rather than the traditional, higher training dose (5.0 mg/kg). It is therefore of interest to evaluate the properties mediating the 1.25 mg/kg CLZ discriminative cue. In the present study, rats were trained to discriminate either 1.25 mg/kg (N=7) or 5.0 mg/kg (N=7) CLZ from vehicle in a two-lever drug discrimination task. The typical antipsychotic haloperidol (0.1-0.4 mg/kg) did not substitute for either CLZ cue, whereas the atypical antipsychotic melperone (0.37-3.0 mg/kg) provided full substitution in both groups (>80% CLZ-appropriate responding). The 5-HT(1A) receptor agonist (+)-8-OH-DPAT (0.04-0.16 mg/kg), and the selective 5-HT(2A) receptor antagonist M100907 (0.03-1.0 mg/kg) did not produce substitution in either group. (+)-8-OH-DPAT combined with haloperidol (0.05 mg/kg) engendered only partial substitution (>60% CLZ-appropriate responding) for both CLZ cues, and M100907 combined with haloperidol (0.05 and 0.1 mg/kg doses) failed to provide substitution in either group. Trihexyphenidyl (0.18-6.0 mg/kg), a muscarinic M(1)-preferring receptor antagonist, engendered full substitution for the 1.25 mg/kg CLZ cue, but only partial substitution for the 5.0 mg/kg CLZ cue. These results provide evidence that antagonism at the muscarinic M(1) receptor is sufficient to provide 1.25 mg/kg CLZ-like discriminative stimulus effects.

Topics: 8-Hydroxy-2-(di-n-propylamino)tetralin; Animals; Antipsychotic Agents; Butyrophenones; Clozapine; Discrimination, Psychological; Dopamine; Dopamine Antagonists; Dopamine D2 Receptor Antagonists; Dose-Response Relationship, Drug; Fluorobenzenes; Generalization, Stimulus; Haloperidol; Male; Muscarinic Antagonists; Piperidines; Rats; Rats, Sprague-Dawley; Receptors, Muscarinic; Serotonin; Serotonin Antagonists; Serotonin Receptor Agonists; Trihexyphenidyl

Preferential increases in both cortical dopamine (DA) and acetylcholine (ACh) release have been proposed to distinguish the atypical antipsychotic drugs (APDs) clozapine, olanzapine, risperidone and ziprasidone from typical APDs such as haloperidol. Although only clozapine and ziprasidone are directly acting 5-HT(1A) agonists, WAY100635, a selective 5-HT(1A) antagonist, partially attenuates these atypical APD-induced increases in cortical DA release that may be due to combined 5-HT(2A) and D(2) blockade. However, WAY100635 does not attenuate clozapine-induced cortical ACh release. The present study determined whether quetiapine, iloperidone and melperone, 5-HT(2A)/D(2) antagonist atypical APDs, also increase cortical DA and ACh release, and whether these effects are related to 5-HT(1A) agonism. Quetiapine (30 mg/kg), iloperidone (1-10 mg/kg), and melperone (3-10 mg/kg) increased DA and ACh release in the medial prefrontal cortex (mPFC). Iloperidone (10 mg/kg) and melperone (10 mg/kg), but not quetiapine (30 mg/kg), produced an equivalent or a smaller increase in DA release in the nucleus accumbens (NAC), respectively, compared to the mPFC, whereas none of them increased ACh release in the NAC. WAY100635 (0.2 mg/kg), which alone did not affect DA or ACh release, partially attenuated quetiapine (30 mg/kg)-, iloperidone (10 mg/kg)- and melperone (10 mg/kg)-induced DA release in the mPFC. WAY100635 also partially attenuated quetiapine (30 mg/kg)-induced ACh release in the mPFC, but not that induced by iloperidone (10 mg/kg) or melperone (10 mg/kg). These results indicate that quetiapine, iloperidone and melperone preferentially increase DA release in the mPFC, compared to the NAC via a 5-HT(1A)-related mechanism. However, 5-HT(1A) agonism may be important only for quetiapine-induced ACh release.

Topics: Acetylcholine; Animals; Antipsychotic Agents; Butyrophenones; Clozapine; Dibenzothiazepines; Dopamine; Haloperidol; Isoxazoles; Male; Microdialysis; Nucleus Accumbens; Piperidines; Prefrontal Cortex; Quetiapine Fumarate; Rats; Rats, Sprague-Dawley; Receptors, Serotonin; Receptors, Serotonin, 5-HT1

The results of a one year treatment with Melperone are reported. 18 mentally retarded female patients with severe aggressive and autoaggressive behaviour had been included in this open study. Six patients suffered from various epileptic seizures. A significant reduction of aggressive and autoaggressive behaviour, measured by the AFGB, was found. The activity of alkaline phosphatase showed a significant tendency towards normalisation. EEG-controls of patients with epileptic seizures showed no increase of epileptic activity in the EEG. No severe side effects were noticed.

Topics: Adolescent; Adult; Aggression; Alkaline Phosphatase; Antipsychotic Agents; Butyrophenones; Electroencephalography; Epilepsy; Female; Humans; Intellectual Disability; Leukocytes; Piperidines

Topics: Butyrophenones; Diazepam; Female; Homovanillic Acid; Humans; Hydroxyindoleacetic Acid; Methoxyhydroxyphenylglycol; Paranoid Disorders; Piperidines; Prolactin; Schizophrenia; Therapeutic Equivalency; Thiothixene

Topics: Action Potentials; Animals; Antipsychotic Agents; Butyrophenones; Chlorpromazine; Guinea Pigs; Haloperidol; Heart; In Vitro Techniques; Membrane Potentials; Myocardial Contraction; Papillary Muscles; Piperidines; Refractory Period, Electrophysiological; Thioridazine

The effects of the two neuroleptics, melperone (a butyrophenone) and thioridazine (a phenothiazine), were compared on the electrical and mechanical activity of isolated rat atria. Both electrically stimulated and spontaneously beating atria were used. Melperone was found to prolong the effective refractory period while the threshold for electrical stimulation i.e. the excitability, was almost unaffected. Thioridazine caused a similar prolongation of the effective refractory period, but also decreased the excitability significantly. In contrast to melperone, thioridazine had a negative inotropic effect. The spontaneous pacemaker activity was depressed and the sinus node recovery time increased to a greater extent after melperone than after thioridazine. The results taken together with other recent data support the hypothesis that melperone may be a type III anti-arrhythmic according to the classification of Vaughan Williams, in contrast to thioridazine which has a quinidine-like action (type I). The results also indicate that melperone in addition to prolonging the effective refractory period, may act as an anti-arrhythmic agent by depressing automaticity.

Topics: Animals; Butyrophenones; Electric Stimulation; Female; Heart; Heart Rate; In Vitro Techniques; Myocardial Contraction; Piperidines; Rats; Refractory Period, Electrophysiological; Sinoatrial Node; Thioridazine; Tranquilizing Agents