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Biomedical subjects

B I Diamond

Publications and source records attributed to B I Diamond.

At least 37 records · Page 2Linked to original sources
PubMed1987

Neuropharmacology of the extrapyramidal system.

The neuropharmacology and neuroanatomy of the extrapyramidal system are complex; however, in its most reductionistic state, this system is often described as a balance between the actions of dopamine and acetylcholine. In this paper, a thorough investigation of the neuroanatomy and neuropharmacology of the extrapyramidal system is undertaken, and an attempt is made to delineate the roles of other neurotransmitters and neuromodulators that play an important role in its functioning. To demonstrate the therapeutic complexity of extrapyramidal system movement disorders, clinical literature is briefly reviewed to show the relative efficacies of anticholinergic and prodopaminergic antiparkinsonian agents in treating neuroleptic-induced extrapyramidal side effects and to show how drugs that affect alternative neurotransmitter systems have also been used to treat these same side effects.

Acetylcholine↗
PubMed1984

Enhancement of hypophysectomy-induced dopamine receptor hypersensitivity in male rats by chronic haloperidol administration.

It has been reported that hypophysectomy (HYPOX) would antagonize the development of a neuroleptic-induced dopamine receptor hypersensitivity, and suggested that the neuroleptic-induced dopamine receptor hypersensitivity may be mediated by the neuroleptic-induced hyperprolactinemia. Conversely, we and others have reported on the ability of HYPOX animals to develop a neuroleptic-induced dopamine receptor hypersensitivity. The present study was undertaken to define the possible role(s) of prolactin in the modulation of striatal dopamine receptor sensitivity. The data from these studies indicate: that HYPOX alone will result in the development of a striatal dopamine receptor hypersensitivity; that the HYPOX-induced dopamine receptor hypersensitivity could be increased by the chronic administration and withdrawal of haloperidol; that administration of prolactin to HYPOX rats would partially antagonize the development of the neuroleptic-induced dopamine receptor hypersensitivity; and that the administration of prolactin alone had minimal effects on the apomorphine-induced behavior or neurochemistry of the HYPOX animals. These results suggest that the neuroleptics do not require the presence of a pituitary secretion (specifically, prolactin) to induce a striatal dopamine receptor hypersensitivity; however, they do indicate that a pituitary secretion, perhaps prolactin, may have the ability to modulate striatal dopamine sensitivity.

Animals↗
PubMed1983

Treatment approaches in Gilles de la Tourette syndrome.

The neurological disorder Gilles de la Tourette syndrome is most often treated with the receptor blocker haloperidol, which also produces multiple side-effects, including the risk for tardive dyskinesia. In placebo control double-blind studies, two other neuroleptic drugs, fluphenazine and trifluoperazine, were found to be as efficaceous as haloperidol, but with fewer side-effects. In other studies, clonidine was shown to be equally efficaceous with haloperidol, but did not produce adverse central nervous system side-effects. To treat the extrapyramidal side-effects accompanying the treatment of Tourette syndrome with neuroleptic agents, amantadine and benztropine were compared in a crossover study. It was demonstrated that amantadine is a superior agent in treating the side effects of haloperidol treatment in Tourette syndrome. The use of lithium was without significant action upon lessening the tics of Tourette syndrome.

Amantadine↗
PubMed1983

Regional selectivity of neuroleptic drugs: an argument for site specificity.

Differences among neuroleptic drugs in their abilities to produce extrapyramidal side-effects have alternatively been ascribed to their inherent anticholinergic effect or their preferential action with particular brain areas. Animal behavioral studies in rats, with the intralimbic or intrastriatal injection of dopamine demonstrate that atypical neuroleptics, i.e., clozapine, thioridazine, show a greater relative preference for blocking dopamine's limbic actions. Studies using the rat model of tardive dyskinesia (neuroleptic-induced behavioral hypersensitivity), suggest that the atypical neuroleptics are again unique. Receptor ligand studies in rat brain and human brain, using 3H-spiroperidol, show that haloperidol produces a preferential blockade of striatal receptor sites, whereas clozapine and thioridazine are most active at limbic sites. Biochemical data in animals and clinical data in man are reviewed to further support the concept of site specificity.

Animals↗
PubMed1981

Hypophysectomy induced hypersensitivity to dopamine: antagonism by estrogen.

Hypophysectomized (HYPOX) or sham HYPOX (SHAM) and ovariectomized rats were injected with either estradiol benzoate (EB, 10 microgram/kg/day x 3) or sesame oil (0.25 ml/kg/day x 3). Twenty hours after the last dose of EB or oil all animals were injected with apomorphine and the resulting stereotypy scored. The HYPOX + oil group was more sensitive to the apomorphine than the SHAM + oil group (ED50 = 0.24 and 0.45 mg/kg, respectively). Treatment with EB resulted in a shift to the right of the dose response curves for both the HYPOX and SHAM groups. The ED50 for the HYPOX group was increased to 0.62 mg/kg, while the SHAM group increased to 0.93 mg/kg. The Bmax values for [3H]spiroperidol binding to striatal membranes were not significantly different for the HYPOX + EB, SHAM + EB, or SHAM + oil groups. However, the HYPOX + oil group was significantly increased (54%) at 7 days post-HYPOX. By 28 days post-HYPOX, the Bmax for the HYPOX animals had increased by 94% relative to SHAM animals. The HYPOX induced increase in dopamine sensitivity could be increased by chronic treatment and withdrawal of haloperidol. The haloperidol induced increase in apomorphine induced stereotypy and [3H]spiroperidol binding could be antagonized by EB treatment during the withdrawal phase of the haloperidol treatment. These data indicate that the pituitary has a modulating effect on striatal spiroperidol binding and apomorphine induced stereotypy, but that its presence is not required for estrogen to suppress the efficacy of dopamine or dopamine agonists.

Animals↗
PubMed1981

Antagonism of dopamine supersensitivity by estrogen: neurochemical studies in an animal model of tardive dyskinesia.

The withdrawal from chronic haloperidol or estradiol benzoate (EB) treatment results in a behavioral supersensitivity to dopamine agonists in ovariectomized rats. On the other hand, the administration of EB during the withdrawal from haloperidol or the continuous treatment with EB will attenuate or prevent the development of a supersensitivity to dopamine agonists. The enhanced behavioral sensitivity to dopamine agonists is correlated with an increase in 3H-dopamine binding sites in striatal membranes. The administration of EB during the withdrawal from chronic haloperidol treatment or the continuous administration of EB decreases or prevents the proliferation of dopamine binding sites in the striatum that normally orccur upon withdrawal of these two substances. These results indicate that exogenous estrogens may modulate the number of dopamine receptors in the central nervous system and, as such, may decreasse the incidence and/or relieve the symptoms of tardive dyskinesia.

Animals↗
PubMed1980

Estrogen in experimental tardive dyskinesia.

Postmenopausal women have the highest incidence of tardive dyskinesia, suggesting that loss of ovarian function may predispose to this condition. Moreover, reports have indicated that estrogens could reduce abnormal movements in tardive dyskinesia. To test the effects of estrogen in tardive dyskinesia, ovariectomized rats were treated daily for 16 days with haloperidol alone (0.5 mg per kilogram) or haloperidol plus estradiol benzoate (EB; 8 microgram per kilogram). Rats were then challenged with apomorphine (0.25 mg per kilogram) 4 and 10 days after cessation of the chronic treatments. Chronic treatment with haloperidol alone enhanced the response to apomorphine, whereas the combined treatment produced a synergistic response. Rats treated chronically with haloperidol and then treated daily with EB after the haloperidol treatment showed an attenuation of drug-induced stereotypy. These data indicate that estrogen may mask development of tardive dyskinesia.

Animals↗