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R F Pfeiffer

Publications and source records attributed to R F Pfeiffer.

At least 73 records · Page 4Linked to original sources
PubMed1990

Clozapine for psychosis in Parkinson's disease.

The clinical efficacy of clozapine, an atypical antipsychotic, in treating levodopa-induced hallucinations was investigated in five patients with Parkinson's disease under open label conditions. Two patients could not tolerate clozapine, even in doses as low as 12.5-25 mg daily, because of extreme sedation. Three patients could tolerate clozapine and experienced improvement or elimination of their hallucinations at doses below 100 mg daily. Despite a significant risk of adverse effects, cautious use of clozapine in low doses may be beneficial for patients with levodopa-induced psychosis who do not respond to more conservative measures.

Aged↗
PubMed1990

Pathogenesis and treatment of neuroleptic malignant syndrome.

1. Neuroleptic drugs (antipsychotics) produce numerous side effects which include serious extrapyramidal symptoms consisting of akathisia, dystonia, neuroleptic malignant syndrome, parkinsonian reactions such as postural abnormality, tremor, akinesia or bradykinesia, rigidity, and tardive dyskinesia. 2. Among the complications of neuroleptic chemotherapy, the most serious and potentially fatal complication is malignant syndrome, which is characterized by extreme hyperthermia, "lead pipe" skeletal muscle rigidity causing dyspnea, dysphagia, and rhabdomyolysis, autonomic instability, fluctuating consciousness, leukocytosis, and elevated creatine phosphokinase. 3. Neuroleptic malignant syndrome should be differentiated from malignant hyperthermia, lethal catatonia, and other pathological states producing some of these same symptoms. 4. In addition to neuroleptics, malignant syndrome has been caused by thymoleptics (antidepressants), metoclopramide (antiemetic), metoclopramide combined with cimetidine, tetrabenazine, overdosage of benzodiazepine, phenelzine, dothiepin and alcohol, and amphetamine. 5. Factors leading to and/or facilitating the emergence of neuroleptic malignant syndromes are reportedly organic brain syndrome, dehydration, exhaustion, external heat load, excessive sympathetic discharge, use of long acting neuroleptics, high doses of neuroleptics, rapid dose titration with neuroleptics, abrupt discontinuation of antiparkinsonism agents, and concurrent lithium therapy. 6. Although, the pathogenesis of neuroleptic malignant syndrome is not understood completely, a blockade of dopaminergic receptors in the hypothalamus, spinal cord and striatum, an alteration of dopaminergic-serotonergic transmission in the body, an enhanced synthesis and action of prostaglandin E1 and E2, and a modification of calcium-mediated signal transduction in the body have been suggested. 7. The treatment of malignant syndrome includes immediate withdrawal of neuroleptic drugs, i.v. infusion of dantrolene, and oral administration of bromocriptine; or alternatively i.v. infusion of dantrolene and the combination of levodopa-carbidopa. 8. Other measures to enhance the therapeutic effectiveness of the aforementioned regimens are to include the use of anticholinergic drugs such as benztropine to enhance the effectiveness of bromocriptine, of lorazepam if catatonic symptoms persist, or of electroconvulsive therapy (ECT) if psychotic symptoms persist. 9. These treatments, however, must be "active" rather than "passive", in order to avert fatalities and/or unfortunate sequelae from this iatrogenic and incompletely understood disease.

Antipsychotic Agents↗
PubMed1990

Hippocampal zinc thionein and pyridoxal phosphate modulate synaptic functions.

The hippocampus, a component of the limbic system, is a prominent subcortical structure, which not only contains high concentrations of zinc, but also exhibits regional variations in this essential element, with concentrations being highest in the hilar region and lowest in the fimbria. For example, the concentration of zinc in the mossy fiber axons has been estimated to approach 300-350 microM. Both zinc and pyridoxal phosphate (PLP) deficiency and excess have been reported to produce epileptiform seizures, which are blocked by gamma-aminobutyric acid (GABA). The proposed mechanism is that at physiological concentrations zinc stimulates the activity of the hippocampal pyridoxal kinase (50% stimulation at 1.7 x 10(-7) M), enhancing the formation of PLP, whereas in pharmacological doses zinc inhibits the activity of glutamate decarboxylase (GAD) directly (50% inhibition at 6.5 X 10(-4) M) by preventing the binding of PLP to HoloGAD. Furthermore, recent studies have shown that two forms of GAD are found in the rat brain. One form (GAD A) does not require PLP for maximal activity, while another form (GAD B) does. Furthermore, the ratio between GAD A and GAD B is nonuniform throughout brain areas, and the hippocampus contains twice as much GAD B (the PLP-requiring GAD) as GAD A. Although the hippocampus is a common target of exogenous neurotoxic agents, "free" zinc in greater than physiological concentrations should be considered an endogenous central neurotoxin. For example, iontophoretically applied zinc in the frontoparietal cortex enhances and prolongs the firing rate of neurons in urethane-anesthetized rat. In addition, zinc (50-500 microM) significantly depresses the paired-pulse potentation in the hippocampal CA3 subfield. Moreover, zinc selectively blocks the action of N-methyl-D-aspartate on cortical neurons and enhances the quisqualate receptor-mediated injury. Finally zinc competitively inhibits the calcium-dependent release of transmitter by inhibiting the entry of Ca2+ into the nerve terminals. Since zinc in a concentration of 300-350 microM could not possibly remain "unbound" in the hippocampus, we searched for and identified a metallothionein-like protein (MT) in the bovine hippocampus, which produces two isoforms on reverse-phase HPLC and lacks aromatic amino acids, but possesses metallomercaptide bonds. We believe that the hippocampal metallothionein, by donating zinc to an extensive number of zinc-activated, PLP-mediated biochemical reactions, modulates synaptic functions. Furthermore, by virtue of its inducibility, metallothionein binds additional amounts of zinc, maintains its steady-state concentration, prevents inhibition of an extensive number of sulfhydryl-containing enzymes and receptor sites, and hence averts metal-related neurotoxicity.

Animals↗
PubMed1989

CQP 201-403 in Parkinson's disease: an open-label pilot study.

The dopamine agonist, CQP 201-403, was administered to 10 patients in an open label fashion with rapid dosage escalation during hospitalization. Assessed over an average of 20 days, significant improvement occurred in bradykinesia, rigidity, and postural instability. Tremor did not occur in sufficient frequency in this group of patients to be accurately assessed. The most serious adverse effect encountered was prolonged confusion with psychosis. This study suggests that CQP 201-403 may be of value in the treatment of Parkinson's disease.

Aged↗
PubMed1989

"On-off"-induced lethal hyperthermia.

Neuroleptic malignant syndrome (NMS) is being increasingly recognized as a potential complication of neuroleptic therapy. Similar hyperthermic episodes have also been described in other settings of abrupt cessation of dopaminergic stimulation such as levodopa withdrawal. We report a fatal NMS-like episode occurring as a complication of an "off" period in a patient with Parkinson's disease.

Antiparkinson Agents↗
PubMed1989

Pontine and extrapontine myelinolysis following liver transplantation. Relationship to serum sodium.

The relationship between central pontine myelinolysis (CPM) and extrapontine myelinolysis (EPM) and serum sodium changes in the setting of orthotopic liver transplantation (OLT) is examined. Postmortem examination of 14 patients with end-stage liver disease who underwent liver transplantation revealed CPM in four, of which three also had EPM. A retrospective review of clinical and laboratory data was performed on all patients. There were marked perioperative rises (21-32 mEq/L) in the serum sodium concentration in all four patients who developed myelinolysis. In contrast, the largest increase in sodium in patients without demyelination was 16 mEq/L. We conclude that perioperative rises in the serum sodium concentration increase the risk of myelinolysis. CPM and EPM should be considered if the patient develops mental status changes or focal neurological deficits several days after OLT.

Adult↗
PubMed1986

Bromocriptine holiday: effects on dopamine receptors and turning behavior in rats.

In experimental Parkinson's disease, we studied the effects of chronic administration (30 days), withdrawal, and reinstitution of bromocriptine. Dopamine (DA) receptor supersensitivity was produced by 6-hydroxydopamine and reversed by chronic bromocriptine administration. Drug holiday reestablished sensitivity of DA receptors, but reinstitution of bromocriptine again downregulated receptors. The effects of a drug holiday on DA receptors are short-lived, and long-term clinical improvement cannot be expected. Apomorphine-induced contralateral turning produced by the lesion was unaffected by any drug regimen.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1985

Low-dose bromocriptine therapy in Parkinson's disease.

The efficacy of low-dose bromocriptine mesylate administration (20 mg daily or less) was evaluated in a double-blind study. Nine of 16 individuals receiving bromocriptine completed the 40-week study. Modest, but significant, improvement was derived from bromocriptine therapy. Improvement was most evident in tremor. Maximum improvement was achieved with doses between 7.5 and 15.0 mg daily, with some decline in efficacy as doses approached 20 mg. Adverse effects were common, but were generally mild in severity. Our results suggest that bromocriptine in low doses may be an effective adjunct to carbidopa and levodopa (Sinemet) in the treatment of Parkinson's disease.

Aged↗
PubMed1985

Mesulergine (CU32-085) in the treatment of Parkinson's disease.

Twenty patients with Parkinson's disease were treated with the 8-alpha-ergoline derivative mesulergine. Participants were divided into two groups, and over a nine-week period, mesulergine dosage was increased to a maximum of either 10 or 20 mg daily. During this time levodopa-carbidopa (LD-CD) dosage was reduced and treatment was discontinued if possible. The dosage of LD-CD was reduced 75% in the 10 mg group and 74% in the 20 mg group. Patients in the low-dose group maintained their functional status and showed improvement in postural stability. Patients in the high-dose group showed improvement in each of the cardinal signs of parkinsonism. Adverse effects were generally mild and infrequent. Many adverse effects induced by LD-CD diminished or resolved. Our results suggest that mesulergine can be valuable in the management of Parkinson's disease, particularly in those individuals experiencing dose-limiting adverse effects from LD-CD.

Aged↗
PubMed1985

Effects of L-dopa supplementation on concentrations of brain catechols, dopamine receptor binding and the incidence of pale, soft and exudative meat in stress-susceptible pigs.

The purpose of this research was to determine if chronic dietary L-DOPA supplementation will alter differentially the brain catechol concentrations, dopamine receptor binding (KD and Bmax) and the incidence of pale, soft and exudative (PSE) meat in stress-susceptible (SS) and stress-resistant (SR) pigs. Stress-susceptible and SR pigs were assigned randomly to these four groups: SS pigs as controls, SR pigs as controls, SS pigs with L-DOPA supplementation and SR pigs with L-DOPA supplementation. The experiment began when pigs weighed 23 kg and terminated when pigs weighed 95 kg. Anatomical brain structures removed at slaughter included hypothalamus, thalamus, cortex, cerebellum, olfactory bulb, caudate nucleus, putamen and substantia nigra. Concentrations of norepinephrine and dopamine were greater in the hypothalami of SS than of SR control pigs. The L-DOPA supplementation eliminated the strain differences of brain catecholamine concentrations. Pigs fed L-DOPA had greater concentrations of dihydroxyphenylacetic acid in six of the eight brain regions analyzed than the controls. Dopamine receptor binding (Bmax and KD) of spiroperidol was similar in all four groups of pigs. Pale, soft and exudative pork developed to the same extent in SS pigs with or without L-DOPA treatment. The results suggest that L-DOPA supplementation eliminates strain differences in brain catecholamine concentrations but does not alter PSE meat development or striatal dopamine receptor binding.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1984

Dopamine receptors: effects of chronic L-dopa and bromocriptine treatment in an animal model of Parkinson's disease.

Male albino rats received a stereotaxic injection of 6-hydroxydopamine (6-OHDA) into the right substantia nigra. Animals demonstrating contralateral rotations 2 weeks postoperatively with apomorphine (0.5 mg/kg i.p.) were treated with L-Dopa (55 mg/kg i.p.), bromocriptine (2 mg/kg i.p.), or polyethylene glycol (vehicle) every 12 h for 30 days. Striatal dopamine (DA) receptors were analyzed by Scatchard plot using 3H-spiroperidol (3H-SP) as ligand. 3,4-Dihydroxyphenylacetic acid (DOPAC) and DA were measured by use of high pressure liquid chromatography. 6-OHDA lesions produced a supersensitivity in striatal DA receptors. Chronic L-Dopa or bromocriptine treatment reversed this supersensitivity. Neither lesion nor drug treatment alone or together produced a significant change in affinity (KD) for 3H-SP. Drug treatment alone also had no effect on Bmax. DA and DOPAC levels were reduced by greater than 98% in lesioned striata. Neither drug treatment affected DA or DOPAC levels as compared with controls. These results indicate that chronic administration of either bromocriptine or L-Dopa will reverse the DA receptor denervation supersensitivity in striatum seen following 6-OHDA lesion. This reversal may play a role in the clinical changes seen in Parkinson's disease patients following chronic use of these drugs.

3,4-Dihydroxyphenylacetic Acid↗