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PubMed1987

Antagonism by neuroleptics of serotonin 5-HT1A and 5-HT2 receptors of normal human brain in vitro.

Using radioligand binding techniques and human frontal cortex, we determined the equilibrium dissociation constants (KDs) of 17 neuroleptics at the serotonin 5-HT1A and serotonin 5-HT2 receptors with [3H]WB4101 and [3H]ketanserin, respectively. At the serotonin 5-HT1A receptor, the most and least potent neuroleptics were chlorprothixene (KD = 230 nM) and fluphenazine (KD = 40 microM), respectively. At the serotonin 5-HT2 receptor, the most and least potent neuroleptics were spiperone (KD = 0.38 nM) and molindone, (KD = 5 microM), respectively.

Antipsychotic Agents↗

PubMed1996

Pharmacological validation of the chronic mild stress model of depression.

Chronic exposure to mild unpredictable stress has previously been found to depress the consumption of palatable sweet solutions, and this effect was reversed by chronic treatment with a variety of antidepressant drugs. The present study reports three experiments examining the effects in this model of further antidepressant agents, a number of non-antidepressants, and some compounds of indeterminate clinical status. Male Wistar rats were exposed sequentially to a variety of mild stressors, which continued throught the experiments. Drug treatments commenced after 3 weeks of stress, by which time intake of a 1% sucrose solution (measured in a 1-h weekly test) was significantly depressed. No drug effects were seen after 1 week of treatment. Normal levels of sucrose drinking were seen following chronic (3-5 weeks) of treatment with the antidepressants imipramine (10 mg/kg per day), brofaromine (20 mg/kg per day), and buspirone (5 mg/kg per day). Positive effects were also seen following chronic treatment with atropine (1 mg/kg per day) and mepyramine (5 mg/kg per day). d-Amphetamine (1 and 3 mg/kg per day), the neuroleptics haloperidol and chlorprothixene (1 mg/kg per day), and morphine (administered at doses rising to 110 mg/kg per day) were ineffective; amphetamine (3 mg/kg) and morphine decreased sucrose intake in control animals. No inferences can be drawn from the effects of atropine and mepyramine, which are of indeterminate clinical status; data from the other seven agents tested support the hypothesis that the chronic mild stress model responds appropriately to antidepressant and non-antidepressant agents.

Animals↗

PubMed1981

Formation of nitroso compounds and mutagens from tranquilizers by drug/nitrite interaction.

The formation of nitroso compounds and mutagens by drug/nitrite interaction was screened for 14 tranquilizers. The drug (0.05 M) was reacted with nitrite (0.5 M) at pH 3-3.5. After 4 h at 37 degrees C, nitroso compound formation was observed for flupentixol, chlordiazepoxide, spiperone, thiothixene, and chlorprothixene in more than 40% yield. Mutagenicity was found in the reaction products of opipramol, chlordiazepoxide, bromazepam, thiothixene, and carpipramine by the Ames assay using Salmonella typhimurium TA98 and TA100 as tester strains.

Drug Interactions↗

PubMed2006

Quantitative determination of forty-eight antidepressants and antipsychotics in human serum by HPLC tandem mass spectrometry: a multi-level, single-sample approach.

This method describes the simultaneous determination of amisulpride, amitriptyline, aripiprazole, benperidol, chlorpromazine, chlorprothixene, citalopram, clomipramine, clozapine, desipramine, doxepin, fluoxetine, flupentixol, fluphenazine, fluvoxamine, haloperidol, hydroxyrisperidone, imipramine, levomepromazine, maprotiline, mianserine, mirtazapine, moclobemide, norclomipramine, nordoxepin, norfluoxetine, nortriptyline, O-desmethylvenlafaxine, olanzapine, opipramol, paroxetine, perazine, perphenazine, pimozide, pipamperone, quetiapine, reboxetine, risperidone, sertraline, sulpiride, thioridazine, trazodone, trimipramine, venlafaxine, viloxazine, ziprasidone, zotepine and zuclopenthixol with a single sample/triple injection approach. Drugs were assigned to subgroups covering low, medium and high concentrations (overall range of therapeutic levels to be considered: 0.5-2000 ng/mL) by further dilution of the supernatant obtained after the first protein precipitation. Chromatographic separation was necessary for isobaric mass fragments and performed on a monolithic C18 column (50mmx4.6mm) with methanol gradient and 5mM acetate buffer at pH 3.9. The injection interval was 8 min. A set of three internal standards was used for quantification of drugs with widely varying hydrophobicity. After electrospray ionization positive ion fragments were detected in the multiple reaction monitoring (MRM) mode with an API 4000 tandem mass spectrometer. Regression parameters of calibration curves and limits of quantification showed good covering of therapeutic and subtherapeutic ranges with an average correlation coefficient of 0.9988. Imprecision and inaccuracy measures were prepared for intra- and inter-assay comparisons at three concentration ranges in all subgroups. Average coefficients of variation were 6.1% for intra-assay and 7.4% for inter-assay comparisons, while average deviations from spiked concentrations were 4.8% for intra-assay and 4.2% for inter-assay comparisons, respectively. Recovery rates, measured as the percent recoveries of spiked serum samples against standard solutions without serum matrix, varied between 92 and 111%, with an average of 101%. As the only exception, the olanzapine response was much higher (185%) in serum matrix than in matrix-free controls.

Antidepressive Agents↗

PubMed2005

Analysis of the antimalarial drug halofantrine and its major metabolite N-desbutylhalofantrine in human plasma by high performance liquid chromatography.

The determination of halofantrine and its major metabolite N-desbutylhalofantrine in human plasma by reversed phase high-pressure liquid chromatography is described. The method involves protein precipitation of plasma samples by acetonitrile followed by basification with sodium hydroxide and subsequent liquid-liquid extraction using hexane-diethyl ether (1:1, v/v). The chromatographic separation was carried out on a C-18 column with a mobile phase consisting of methanol/0.05 M KH2PO4 (78:22, v/v) containing 55 mM perchloric acid. Chlorprothixen was used as internal standard. The relative standard deviations of intraday and interday precision for both compounds were less than 7%, the relative standard deviation of the accuracy did not exceed 7.1% at concentrations of 50 and 300 ng/ml. This method is simple, rapid, sensitive and cost effective and was applied to the determination of the pharmacokinetics of halofantrine and N-desbutylhalofantrine in two healthy male volunteers after an oral administration of 500 mg halofantrine. Moreover, the influence of the frequently consumed kolanut on the pharmacokinetics of halofantrine was investigated.

Antimalarials↗

PubMed1999

Pharmacological profile of neuroleptics at human monoamine transporters.

Using radioligand binding techniques, we determined the equilibrium dissociation constants (K(D)) for 37 neuroleptics and one metabolite of a neuroleptic (haloperidol metabolite) for the human serotonin, norepinephrine, and dopamine transporters with [3H]imipramine, [3H]nisoxetine, and [3H]WIN35428, respectively. Among neuroleptics, the four most potent compounds at the human serotonin transporter were triflupromazine, fluperlapine, chlorpromazine, and ziprasidone (K(D) 24-39 nM); and at the norepinephrine transporter, chlorpromazine, zotepine, chlorprothixene, and promazine (K(D) 19-25 nM). At the human dopamine transporter, only pimozide (K(D) = 69+/-3) ziprasidone (K(D) = 76+/-5) had notable potency. These data may be useful in predicting therapeutic and adverse effects, including drug interactions of neuroleptics.

Antipsychotic Agents↗

PubMed2002

Detection of antidepressant and antipsychotic drugs in human hair.

The presence of therapeutic drugs and their metabolites in the hair of psychiatric patients was investigated using gas chromatography (GC)-mass spectroscopy (MS)-electron ionization (EI) and GC-MS-chemical ionization (CI). In hair samples tested from 35 subjects, carbamazepine, amitriptyline, doxepin, trihexyphenidyl, chlorpromazine, chlorprothixene, trifluoperazine, clozapine and haloperidol were detected, with maximal concentrations of 22.5, 57.7, 183.3, 15.6, 68.2, 30.0, 36.8, 59.2 and 20.1 ng/mg of hair sample, respectively. Chlorpromazine and clozapine concentrations in the hair were found to be dependent on the dosage used and their correlation coefficients were 0.8047 (P<0.001, n=16) and 0.7097 (P<0.001, n=16), respectively. Segmental analysis demonstrated that there was a correlation between the history of subject's drug exposure and the distribution of drug along the hair shaft. Our results also show that drug analysis in hair may provide useful information about drug treatment and the history of usage, and that drugs can be detected in normally kept hair for at least 16 months after intake.

Adult↗

PubMed1997

Effect of pigmentation on the drug deposition in hair of grey-haired subjects.

The hair samples of 15 grizzled patients with a permanent medical treatment by amitriptyline, carbamazepine, chlorprothixene, diclofenac, doxepine, indomethacine, maprotiline or metoclopramide, or with a chronic heroin and cocaine abuse were separated into white and pigmented fibers and both fractions were independently investigated by GC-MS. The drugs were found in pigmented fibers as well as in white fibers, but the concentrations in the white fibers were smaller than in the pigmented ones for the most of the samples investigated. The concentration ratio of the drugs or their metabolites in both hair fractions (white/pigmented) was found to be between 0.09 and 1.57 (mean 0.70, 30 concentration pairs). There are large differences in this ratio between different subjects with the same drug, whereas for different drugs in the same subject in many cases similar ratios were measured. As a reason a different grade of pigmentation of the hair and the influence of the drug structure are discussed. From these results it follows that the natural hair colour is an important parameter in the evaluation of drug concentration in hair.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1997

Exhumations: synopsis of morphological and toxicological findings in relation to the postmortem interval. Survey on a 20-year period and review of the literature.

Before an exhumation the question of its possible success usually arises. This paper aims to act as an aid by providing comprehensive lists ("expectation catalogues") of morphological and toxicological findings with their corresponding postmortem intervals. All organ systems are included. The results are based on the retrospective evaluation of 46 exhumations performed at the Cologne Institute of Forensic Medicine in a 20-year period (1974-1994) and a review of the literature. In our own material (34 males, 12 females, age range: 2 days-91 years) the postmortem interval varied from 6 days to 20.5 years. Exhumations were performed by order of criminal courts (n = 28), social insurances (n = 13) and private persons (n = 5). Main indications were problems of causality in social and civil law (n = 14), suspected intoxications (n = 10), possible medical malpractice (n = 7), criminal aspects of traffic accidents (n = 7) and identifications (n = 5). The expectation catalogues include the following remarkable items (with postmortem interval) from our own material: coronary thrombosis (3.5 months), granulation tissue in myocardial infarction (3.5 months), myocardial fibrosis (2.5 years), coronary sclerosis (7.5 years), femoral vein thrombosis and pulmonary embolism (3.75 months), pneumonia (3 months), pulmonary emphysema and chronic bronchitis (2.5 years); detection of strangulation marks (2 months); preservation of bone marrow histology (3 months), gastrointestinal tract in continuity (7.5 years), macroscopic and histological cerebral structures (17 years); toxicological detection of phenobarbital (6 weeks), CO-Hb (9.5 weeks), chlorprothixene (5.5 years), diazepam (7.5 years), furosemide (7.5 years) and parathion (E 605) (17 years). The cause of death could be clarified with sufficient certainty in 36/46 cases (78%). Exhumation problems could be answered completely in 39 cases and partly in seven further cases. On the whole this review again underlines the importance and value of this special kind of body examination even after long postmortem periods.

Academies and Institutes↗

PubMed2003

The use of the new SPE methods for isolation of some tricyclic antidepressant drugs from human serum.

Solid-phase extraction (SPE) methods were applied to isolation of amitriptyline (AMI), imipramine (IMI) and chlorprothixene (CPX) from blood human serum. SPE was carried out using the octadecyl (C(18)) column for isolation of AMI and cyclohexyl (CH) columns in the case of IMI and CPX. The spiked serum samples were used to examine the recoveries of these drugs from C(18) and CH sorbent materials. The volume of serum sample was 500 microl. The recoveries of SPE method using CH cartridge were 100.3+/-1.63% (n=7), 99.7+/-2.3% (n=9) for IMI and CPX, respectively. The recovery of AMI from C(18) cartridge was 99.5+/-1.5% (n=8). Finally, after SPE sample clean-up step the antidepressant drugs were assayed by the own extractive-spectrophotometric methods.

Antidepressive Agents, Tricyclic↗

PubMed2000

Fluorimetric determination of some thioxanthene derivatives in dosage forms and biological fluids.

A simple and highly sensitive method is proposed for the fluorimetric determination of four thioxanthene derivatives, namely: chlorprothixene, clopenthixol, flupentixol and thiothixene, in dosage forms and biological fluids. The method involves the use of nitrous acid as an oxidant to produce the corresponding fluorescent thioxanthenone sulphoxides. The experimental parameters were carefully studied and incorporated into the procedures. The results obtained compare favourably with those obtained by the official methods. The concentration-fluorescence plots were rectilinear over the range of 0.04-0.4 microg/ml for thiothixene, and 0.02-0.25 microg/ml for the other compounds, with minimum detectability (S/N = 2) of 2 ng/ml for all the studied compounds except thiothixene which was 4 ng/ml. The proposed method was applied to the determination of the studied compounds in dosage forms. The results obtained were in good agreement with those obtained adopting the USP XIII method. The proposed method was further applied to the determination of flupentixol in spiked human urine and plasma, the percentage recoveries were 94.39 +/- 1.81 and 96.46 +/- 0.28, respectively. A proposal of the reaction pathway was presented.

Dosage Forms↗

PubMed2001

Different fatal toxicity of neuroleptics identified by autopsy.

Autopsies and toxicological analyses at the Institute of Forensic Medicine revealed 85 fatal intoxications with neuroleptics in Vienna from 1991 to 1997. A total of 17 cases were linked to a single neuroleptic (NL) alone, while 68 deaths were attributed to a combination of NLs with other drugs. The most frequently detected agent was prothipendyl (n=41). During the study period the number of defined daily doses of high-potency NLs prescribed increased significantly (P< or =0.001) due to increased prescribing of new atypical antipsychotics. The quantity of intermediate- and low-potency NLs dispensed remained stable. The most frequently prescribed NL was haloperidol. The relative toxicities of different NLs were calculated by dividing the number of deaths caused by this NL into the number of defined daily doses prescribed in the observation period (f-value). Single-substance intoxications and multiple-substance intoxications were distinguished. The highest f-values were associated with low-potency NLs, especially with prothipendyl, chlorprothixene and levomepromazine. Low f-values were found for the group of high-potency NLs, including flupentixol, fluphenazine, haloperidol and pimozide, as well as olanzapine. Compared to the f-values for all NLs prescribed, f-values for low-potency NLs were shown to be significantly higher concerning single-substance intoxications (P< or = 0.05) and multiple-substance intoxications (P < or = 0.001), while f-values for high-potency NLs were significantly lower (P< or = 0.05 and P< or = 0.001). We are not aware of the psychiatric diagnoses in our post-mortem sample. However, the present results indicate that careless use of low-potent NLs should be avoided in patients with a potential risk of accidental or suicidal overdose.

Adult↗

PubMed1998

Clozapine and several other antipsychotic/antidepressant drugs preferentially block the same 'core' fraction of GABA(A) receptors.

Clozapine and several other antipsychotic/antidepressant drugs that fully or partially block GABA(A) receptors were tested at concentrations that reversed the inhibitory effect of 1 microM GABA on 35S-t-butylbicyclophosphorothionate ([35S]TBPS) binding to rat forebrain membranes only about 20-30%, here designated "core" fractions. Clozapine at 10 microM reverses 1 microM GABA 25+/-4.0% (n = 23) (its "core" fraction). Fourty three compounds were tested alone, and pairwise together with 10 microM Clozapine. The "core" fractions of some of the compounds yielded significant additive reversals together with 10 microM Clozapine, while others did not. A group of 14 compounds of which 7 are clinically effective antipsychotic drugs, including Chlorprothixene, Clomacran, Clopipazan, Fluotracen, Sulforidazine, Thioproperazine, and cis-Thiothixene, were statistically non-additive with 10 microM Clozapine, suggesting that all of these drugs selectively block the same core population of GABA(A) receptors as Clozapine. These non-additivities also suggest that Clozapine at 10 microM fully saturates a subset of GABA(A) receptors blocked by 1 microM GABA. Therefore, Clozapine probably blocks 2 or more types of GABA(A)receptors, but only half of the receptors that are sensitive to 1 microM GABA. A second group of 12 compounds of which 6 are clinically active antidepressant/antipsychotic drugs including Amoxapine, Clothiapine, Dibenzepine, Inkasan (Metralindole), Metiapine and Zimelidine were slightly, but significantly, additive with Clozapine suggesting that these compounds block most of Clozapine's core fraction, plus a small additional fraction. A third group consisted of ten compounds that yielded larger (R > 80) and statistically highly significant additivities with Clozapine. Complete additivity was obtained with Bathophenanthroline disulfonate, and Isocarboxazid, suggesting that they block GABA(A) receptors other than those blocked by 10 microM Clozapine. Seven "classical" GABA(A) receptor blockers, also tested at concentrations yielding 21 to 33% reversal alone, were all significantly additive with 10 microM Clozapine, but in no case was the additivity complete. The largest additivity was obtained with Pitrazepine (21%) and the smallest with Tubocurarine (9%). These results provide further support for the notion that selective blockade of the same subset of GABA(A) receptors may contribute to the clinical antipsychotic/antidepressant effects of Clozapine. The deltaB(opt) values for Clozapine are 50+/-1.7% and 26+/-2.6% (n = 3) in whole rat forebrain and cerebellum, respectively, confirming that clozapine-sensitive GABA(A) receptors are unevenly distributed in the brain. The sedative and anxiolytic properties of Clozapine and other antipsychotic drugs may be due to selective blockade of GABergic disinhibition at certain interneurons.

Animals↗

PubMed1995

[The neuroleptic malignant syndrome].

HISTORY AND CLINICAL FINDINGS: A 22-year-old oligophrenic patient had on several occasions over several months been given various neuroleptics (haloperidol, benperidol, levomepromazine) for exacerbations of paranoid schizophrenia. For a few days before hospitalization he had become quiet and withdrawn, but on the day of admission 100 mg chlorprothixene was administered intramuscularly when he had become agitated. At admission he was somnolent, his general condition was disturbed. He had hyperhidrosis and hypersalivation, as well as tachycardia (112/min) with a normal body temperature of 37.8 degrees C. He also exhibited the cogwheel phenomenon of the limbs and neck, as well as tremor of the hands. The differential diagnosis included inflammatory disease of the brain, sinus thrombosis and, especially, malignant neuroleptic syndrome and febrile catatonia. INVESTIGATIONS: The activities of creatine kinase (3840 U/l), GOT (75 U/l) and GPT (88 U/l) were all increased. Serum myoglobin was 77 micrograms/l. CSF contained blood and there was pleocytosis of 50/3 cells. The ECG showed sinus tachycardia. EEG, chest radiogram, computed tomography, magnetic resonance imaging and cerebral angiography showed no abnormalities. Febrile catatonia could not be excluded. TREATMENT AND COURSE: 4 hours after admission the patient began to respond with normal orientation. Shortly afterwards he was able to walk a few steps, i.e. there was no catatonia. But rigor, tremor, hypersalivation and tachycardia persisted and 12 hours later he developed a fever (up to 39.2 degrees C). Blood pressure varied with peak pressures up to 190/110 mm Hg. After 2 days muscle tone had clearly increased so much that voluntary movement was hardly possible. After amantadine administration (200 mg daily) the rigor improved and for the first time body temperature became normal again. There were no signs pointing to psychotic symptoms. CONCLUSION: Neuroleptic malignant syndrome is difficult to distinguish from febrile catatonia and the diagnosis can often only be made through the clinical course.

Adult↗

PubMed1994

Relevance of drug-melanin interactions to ocular pharmacology and toxicology.

In melanocytes, the biosynthesis of L-dopa derived indole polymer, melanin, is accelerated by tyrosinase and related enzymes. The brown to black pigment is characterized by a stable free-radical property. In humans, a pigment dependent slow onset of ocular actions of ephedrine, atropine, cocaine, pilocarpine and related medications was observed. Extensive accumulation of drugs by melanin appears to be the most important factor governing the long term therapeutic/toxicological activities. Drugs crossing placental circulation are localized in the mouse fetal eye. Thus, drugs exhibit a high binding capacity for melanin containing tissues. Studies on synthetic melanin and melanin granules also indicated a high binding capacity of many therapeutic classes of drugs, including psychotropics. In addition to the liposoluble property of the molecule, there is a definite relationship between chemical structure and the affinity of drugs for melanin. For example, the affinity of chlorpromazine for melanin is higher than that of chlorprothixene. NMR studies, with soluble melanins indicate that there is a steric preference among ephedrine enantiomers. A high binding capacity indicates that more than two molecules of (-)-ephedrine may complex with one indole unit of melanin. Ocular drug development calls for the study of qualitative and quantitative aspects of drug-melanin interaction.

Animals↗

PubMed1986

Binding of ligands to horse liver alcohol dehydrogenase lacking zinc ions at the active sites.

The zinc-deficient enzyme binds the fluorescence probes for the enzyme substrate pocket (auramine O, 13-ethylberberine, chlorprothixene and acridine orange) more tightly than the native enzyme, whereas 1-anilinonaphthalene 8-sulphonic acid is bound with comparable affinity. The use of fluorescence probes as reporter ligands revealed that the formation of binary complexes between the zinc-deficient enzyme and aldehydes is possible (as with the native enzyme) and confirmed an increased affinity of coenzymes to the modified enzyme. The absence of catalytic zinc ions brings about a loss of the essential stabilization effect in simultaneous NADH and aldehyde binding to liver alcohol dehydrogenase. 2,2'-Bipyridine, which chelates the active-site zinc ion in the native enzyme, is bound rather loosely to the same site as aldehydes, auramine O and ethylberberine in the case of the zinc-depleted enzyme. The stopped-flow measurements showed that the pH dependence of auramine O and ethylberberine binding to native and zinc-depleted enzyme is essentially similar. These data are compatible with the presence of ionizable groups in the surroundings of the bound probes. This group might be either His-67, bound to the zinc ion, or the zinc-liganding water molecule in the case of the native enzyme (pK close to 9), or the free His-67 residue in the case of the zinc-deficient enzyme (pK about 8).

2,2'-Dipyridyl↗

PubMedDate not supplied

Efficacy of novel antimicrobials against clinical isolates of opportunistic amebas.

We examined the effects of the macrolide antimicrobial agent azithromycin and phenothiazine compounds against clinical isolates of Acanthamoeba spp. and Balamuthia mandrillaris, opportunistic pathogens of human beings and other animals. Acanthamoeba growth was inhibited in vitro at 1, 5, and 10 micrograms/ml of azithromycin, but not the macrolides, erythromycin, and clarithromycin. In experiments attempting to simulate in vivo conditions, azithromycin protected monolayers of rat glioma cells from destruction by Acanthamoeba at a concentration of 0.1 microgram/ml, and delayed destruction at concentrations of 0.001 and 0.01 microgram/ml. We concluded that the minimal inhibitory concentration of azithromycin was 0.1 microgram/ml. Our results, however, suggested that the drug was amebastatic but not amebicidal, since ameba growth eventually resumed after drug removal. The phenothiazines (chlorpromazine, chlorprothixene, and triflupromazine) inhibited Acanthamoeba growth by 70-90% at 5 and 10 micrograms/ml, but some of these compounds were toxic for rat glioma cells at 10 micrograms/ml. Azithromycin was not very effective against B. mandrillaris in an in vitro setting, but was amebastatic in tissue culture monolayers at concentrations of 0.1 microgram/ml and higher. Balamuthia amebas showed in vitro sensitivity to phenothiazines. Ameba growth was inhibited 30-45% at 5 micrograms/ml in vitro, but completely at 5 micrograms/ml in the rat glioma model. In spite of their potential as antiamebic drugs in Balamuthia infections, toxicity of phenothiazines limits their use in clinical settings.

Acanthamoeba↗

PubMed1977

Antiparkinsonian agents and long-term neuroleptic treatment. Effect of G 31.406, orphenadrine, and placebo on parkinsonism, schizophrenic symptoms, depression and anxiety.

The need for medication with anticholinergic antiparkinsonian drugs was examined in 118 schizophrenic patients under long-term neuroleptic treatment. It was found that 1) none of 18 patients under treatment with low mg potency neuroleptics (chlorprothixene, clozapine, and thioridazine) had any need for anticholinergics; 2) of 60 patients under treatment with short-acting high mg potency neuroleptics (perphenazine greater than 16 mg daily and haloperidol greater than 2 mg daily) nine patients (15%) required medication with anticholinergics, whereas 3) of 40 patients under treatment with long-acting (depot) neuroleptics, 17 (43%) had a need for anticholinergic medication; and 4) no patient factors predisposing to the need for continued antiparkinsonian treatment could be identified. In an additional double-blind cross-over study of 12 patients presenting persisting neuroleptic-induced parkinsonism, it was found that G 31.406 (a new potentially antiparkinsonian drug), compared with placebo, had an antiparkinsonian effect (P less than 0.01) as well as an antidepressant effect (P less than 0.05). G 31.406 resulted in an improvement in anxiety and schizophrenia-score in some patients. Compared with placebo, orphenadrine had a more questionable effect on parkinsonism (0.05 less than P less than 0.01) and no significant effect on mental symptoms. There were no significant differences between the effects of G 31.406 and orphenadrine.

Administration, Oral↗