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Biomedical subjects

J Gerlach

Publications and source records attributed to J Gerlach.

At least 19 recordsLinked to original sources
PubMed1992

Effect of D1 and D2 agonists in primates withdrawn from long-term treatment with haloperidol: the potential role of dopamine D1 receptors in dyskinesia.

The effects of dopamine (DA) D1 and D2 receptor agonists were evaluated in eight Cebus apella monkeys. The monkeys had previously received haloperidol for 2 years, and five of the monkeys had developed mild oral dyskinesia. SKF 81297 (a full D1 agonist) induced marked oral hyperkinesia, consisting of tongue protrusions and licking or chewing movements, most pronounced in the monkeys with pre-existing oral dyskinesia. SKF 38393 and SKF 75670 (partial D1 agonists) also induced some oral dyskinesia, but to a lesser extent than SKF 81297, and with few licking movements. The partial D1 agonists, but not the full agonist, induced sedation. All of the D1 agonists induced grooming behavior, the full D1 agonist to the greatest extent. In the case of SKF 81297, the grooming was closely associated with the licking behavior. Quinpirole (a selective D2 agonist) and apomorphine (a mixed D1/D2 agonist) induced a hyperactive syndrome (nonoral stereotypy with rapid repetitive movements and increased arousal and locomotor activity). Quinpirole induced no grooming behavior and reduced pre-existing oral movements. The data indicate behavioral differences between D1 and D2 receptors and suggest that D1 receptors may be involved in the pathophysiology of some forms of dyskinesia syndromes.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1979

Sulpiride in tardive dyskinesia.

Tardive dyskinesia can be suppressed by drugs that block dopaminergic receptors, but often at the cost of a concomitant increase in parkinsonism. Sulpiride (400 -- 2100 mg/day), a selective type-2 dopamine receptor antagonist, was evaluated in a blind, placebo-controlled trial in 11 patients with tardive dyskinesia. It significantly (P less than 0.01) reduced tardive dyskinesia without significantly affecting parkinsonism, although three patients had a increase in preexisting parkinsonian hypokinesia and tremor. During the placebo phase, the tardive dyskinesia and parkinsonian scores returned to the pretreatment values. There was no relationship between either tardive dyskinesia or parkinsonism and eye blinking rates. These results are consistent with the hypothesis that more than one population of dopamine receptors are involved in controlling extrapyramidal function. Sulpiride is an important tool for elucidating both the practical and heuristic aspects of subtypes of dopamine receptors and is a lead in the search for compounds that selectively affect dopaminergic mechanisms.

Aged↗
PubMed1979

Neuroleptic-potentiating effect of alpha-methyl-p-tyrosine compared with haloperidol and placebo in a double-blind cross-over trial.

The hypothesis that schizophrenia results from overactive dopaminergic influences suggests that reducing dopamine synthesis may increase the clinical effects of dopamine receptor blocking neuroleptic drugs. The neuroleptic potentiating role of alpha-methyl-paratyrosine (AMPT), a tyrosine hydroxylase inhibitor, was compared with haloperidol and placebo in a double-blind cross-over trial. Both AMPT and haloperidol increased the anti-schizophrenic effect of neuroleptic treatment in reduced dose compared with placebo (P less than 0.05), though two patients relapsed during the AMPT period. Both drugs slightly increased extrapyramidal symptoms, but the effect was greater with haloperidol. The limited antipsychotic effect and the potential for aggravating neurological symptoms suggest that the combination of AMPT and neuroleptics does not offer a superior advantage to treating schizophrenia. AMPT, however, may still be used as a research tool in elucidating pathogenetic mechanisms.

Adult↗
PubMed1978

Effect of baclofen on tardive dyskinesia.

Eighteen chronic psychiatric patients with neuroleptic-induced tardive dyskinesia of 1/2-9 years duration participated in a double-blind crossover study on the effect and side effects of baclofen and placebo in the treatment of tardive dyskinesia. Each treatment phase lasted 3 weeks. Evaluation of the results included an assessment of video-tape recording. Baclofen (20-120 mg daily) reduced the hyperkinesias (median score from 5 to 3, P less than 0.05) and increased the parkinsonism (median score from 5 to 7, P less than 0.01). The effect on the oral movement pattern of tardive dyskinesia was characterized by a reduced frequency, an unchanged or slightly reduced amplitude, and an increased duration of each separate mouth opening and tongue protrusion, a response pattern very similar to the response pattern of alpha-methyl-p-tyrosine, an inhibitor of the catecholamine synthesis. Sediation, muscular weakness, and confusion were observed in 50% of the patients. These side effects, appearing mainly in elderly patients, sometimes set in before the anti-hyperkinetic effect, thus limiting the practical usefulness of baclofen in the treatment of tardive dyskinesia.

Aged↗
PubMed1977

[Cortical blindness, clinical, psychologic, and localizatory findings (author's transl)].

Description and evaluation of a case in which both occipital lobes of the brain and adjacent temporal and parietal areas were heavily damaged by malignant meningiomas. Loss of simple and complex visual functions resulted. During a 5-year period the clinical, neurologic, ophthalmologic, and psychologic findings could be completed by self-observation by the highly intelligent patient and compared with findings from three operations. Postmortal neuropathologic analysis showed loss of both left and right areas 17 and 18 and of right area 19. The localizations of elementary and complex visual functions in the brain are discussed.

Aged↗
PubMed1977

Relationship between tardive dyskinesia, L-Dopa-induced hyperkinesia and parkinsonism.

In a study of 16 psychotic patients with neuroleptic-induced tardive dyskinesia and 16 patients with Parkinson's disease and L-Dopa-induced hyperkinesia it was found that (1) tardive dyskinesia, compared to L-Dopa hyperkinesia, was localized almost exclusively to the oral region (P mean value of 0.01), whereas theL-Dopa hyperkinesia was more pronounced in the neck (P mean value of 0.05) and the extremities (P mean value of 0.05); (2) L-Dopa hyperkinesia showed an increasing tendency to oral preponderance with age, irrespective of the severity ofParkinsonism and extra-oral hyperkinesia, while tardive dyskinesia only itensified with age, without any change in distribution; and (3) extra-oral L-Dopa hyperkinesia was related to the localization and severity of pretreatment Parkinsonism, and more to bradykinesia than to rigidity and tremor. It is concluded that the irreversible neurotoxic effect of neuroleptic drugs may be associated with age-related changes in the oral somatotopic region of the basal ganglia (to be given consideration in any future search for the pathogenetic process underlying irreversible tardive dyskinesia), and that the pathophysiology of involuntary hyperkinesia in neuroleptic-treated psychiatric patients and in L-Dopatreated parkinson patients may consist of a primary dopamine deficiency (pharmacological or structural), and a secondary relative hyperactivity in the dopaminergic system ("dopaminergic hypersensitivity") possibly corresponding to hypoactivity in the cholinergic system.

Adult↗
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↗
PubMed1977

The relationship between parkinsonism and tardive dyskinesia.

The author analyzes parkinsonism and hyperkinesia in psychiatric patients with tardive dyskinesia before and during treatment with alpha-methyl-p-tyrosine (AMPT, a dopamine antagonist), biperiden (an acetylcholine antagonist), and baclofen (a GABA agonist); and in patients with paralysis agitans and L-dopa-induced hyperkinesia. AMPT and baclofen had similar influences on oral dyskinesia, resulting in reduced frequency, unchanged or slightly reduced amplitude, and increased duration of each movement. The author concludes that: 1) reduced dopaminergic activity may be the primary pathogenetic background for tardive dyskinesia; 2) dopaminergic hypersensitivity and/or cholinergic hypofunction is necessary before hyperkinesia breaks through; and 3) the neurotoxic effects of neuroleptics may be associated with age-dependent changes in nigrostriatal regions representing oral innervation.

Age Factors↗