Audiological and vestibulo-oculomotor findings in workers exposed to solvents and jet fuel.

Three groups of subjects with long-term (5-41 years) occupational exposure to industrial solvents have been evaluated with extensive audiological and vestibular test batteries. Group A comprised 16 subjects with a confirmed diagnosis of psycho-organic syndrome (POS), while group B consisted of 7 subjects with suspected POS. Both groups had been exposed to mixtures of aliphatic and aromatic solvents. Eight subjects with long-term exposure to jet fuel constituted group C. In the audiological test battery, discrimination of interrupted speech and evoked cortical potentials in response to frequency glides were the tests that yielded significantly abnormal results. In the vestibular test battery, considerable pathology was seen in electronystagmography, and in addition, visual suppression test and saccade test indicated CNS disturbance. In general, when a test yielded pathological results, the incidence of pathology was highest in group A and lowest in group C.

Kainate and glutamate neurotoxicity in dependence on the postnatal development with special reference to hippocampal neurons.

The particular vulnerability of hippocampal CA3/CA4 neurons to intracerebroventricularly administered kainate did not occur in rats until postnatal day 16. Glutamate applied in the same way failed to show comparable neurodegenerative signs, even when administered in large doses to adult animals. Alternatively, both kainate and glutamate exerted similar behavioral effects from postnatal day 15 onwards. No correlation appears between kainate/glutamate-induced behavioral changes and their neurodegenerative potency.

Organic lead encephalopathy: behavioral change and movement disorder following gasoline inhalation.

A 15 year old boy was evaluated in the psychiatric emergency room for the acute onset of "confusion,"insomnia, headache, and shaking of one week's duration. Two days later hallucinations, formication and a movement disorder emerged characterized by action tremor, myoclonus, chorea and ataxia. Further history revealed inhalation of gasoline for its euphoric effects. Plasma lead levels were in the toxic range. Chelation therapy reversed the clinical symptoms. Behavioral changes and a movement disorder in the context of gasoline inhalation are highly suggestive of organic lead encephalopathy. Recognition of this syndrome is important as chelation therapy is effective.

Experiences with a new ergoline (CF 25-397) in parkinsonism.

Studies on rats with unilateral nigral lesions suggest that a new ergoline, CF 25-397, is a dopaminergic agonist that might improve parkinsonism. CF 25-397 induces less stereotyped behavior than other dopaminergic agents in rats, and might therefore cause less dyskinesia than levodopa in man. We investigated the clinical actions of CF 25-397 in nine patients. During treatment, severe deterioration resulted in hypokinesia and rigidity; five patients showed marked dysphagia and dysphonia. There was statistically significant deterioration in four timed tests. Mild improvement, not statistically significant, was noted in tremor. These results indicate that clinical implication of the response to potential therapeutic agents in rodent models of parkinsonism must be interpreted with caution.

[Chemical and pharmacologic study on pyran derivatives. IX. Synthesis of 2-dialkylaminochromones]. / Ricerche chimiche e farmacologiche su derivati piranici. Nota IX. Sintesi di 2-dialchilamminocromoni.

Under suitable conditions the reaction of phenol and N,N-dialkylethoxycarbonylacetamides, in the presence of phosphorus oxychloride, resulted in the formation of 2-dialkylaminochromones. In a similar manner, variously substituted phenols afforded 2-dialkylaminochromones with substituents in different positions of the benzene ring. Pharmacological screening of all these compounds showed that they markedly affect the CNS, activity being mainly excitatory. Decreased activity was shown by compounds with particular substituents in the positions 6,7,8 among which two products [(V e) - K 12440, (V s) - K 12420] have weak but clear anticonvulsant effect.

Screening hallucinogenic drugs: systematic study of three behavioral tests.

The effects of several hallucinogenic and non-hallucinogenic drugs have been studied on three behavioral tests proposed as useful indexes of hallucinogenic activity: "head-twitching" in mice, defecation in an open-field, and suppression of responding on a differential reinforcement of low rates (DRL) schedule of reinforcement. According to the original propositions, after administration of hallucinogenic agents the frequency of head-twitches would increase in mice, the defecation of rats in an open field would decrease without consistent change in ambulation, rearing and grooming, and the responding of rats on a DRL schedule would yield a typical cumulative record pattern. It was found that the head-twitch test was sensitive to mescaline and LSD-25, but not to delta9-THC or to myristicin and elemicin. Besides, the data on interobserver agreement suggested there is a high degree of subjectivity involved in assessing this response. In the open-field test, non-hallucinogenic drugs such as chlorpromazine and apomorphine fell into the hallucinogenic pattern proposed. In addition, the post-injection interval selected seemed to critically affect defecation scores. The DRL "hallucinogenic" pattern occurred nonspecifically after administration of hallucinogenic and non-hallucinogenic drugs. It was concluded that the three tests have limited value for screening purposes.

Observations on the psychopharmacology of the aged.

Psychotropic drugs are discussed under the descriptive categories of antipsychotic, antidepressive, antimanic, anti-anxiety, and cognitive acting. In the antipsychotic classification, special attention is given to side effects (extrapyramidal motor signs, tardive dyskinesias, akathisis) and to dosage for the elderly. The section on congenitive acting drugs includes some pertinent observations on cognitive ability in the aging, the importance of correct diagnosis, and therapeutic strategy. The aged are a population at risk for not only disease, but iatrongenic illness due to direct and indirect drug action. Rational therapy involves understanding the underlying dynamics of the disease and thus the selection of the most effective treatment. Psychotropic drugs in an appropriate program are valuable therapeutic assets.

Apomorphine and piribedil in rats: biochemical and pharmacologic studies.

We studied the biochemical and pharmacologic modes of action of piribedil and apomorphine in the rat. Although both drugs have many points in common, they are also different in many of their manifestations. Apomorphine causes high-intensity, short-duration stereotyped behavior; it is distributed within the brain in uneven fashion, the striatum being the area of lowest concentration as measured by fluorometry. Direct stereotactic injection within the dopaminergic mesolimbic system, and particularly the tuberculum olfactorium, produced constant intense responses. All effects of apomorphine can be blocked by pimozide, but propanolol, a beta blocker, only reduces aggression and ferocity, leaving stereotyped behaviors intact. Finally, L-5-HTP tends to reduce aggression, ferocity, and to a lesser extent stereotypy; MIF or piribedil, as well as reserpine, potentiates the stereotyped behaviors induced by apomorphine, whereas L-DOPA usually decreases them. Piribedil, on the other hand, causes low-intensity, long-duration stereotyped behavior. It is distributed within the brain almost uniformly. Most effects of piribedil can be blocked by pimozide, but propanolol blocks only aggression and ferocity, leaving stereotyped behaviors intact. On the other hand, clonidine, an alpha-receptor agonist, blocks stereotyped behaviors induced by piribedil but markedly increases aggression, ferocity, and motor activity. L-5-HTP and L-DOPA have little effect on piribedil-induced manifestations. Reserpine decreases piribedil stereotypy. The main metabolite of piribedil, S 584, had no clear-cut pharmacologic action in our hands at the dosage used. It is concluded that both apomorphine and piribedil produce stereotyped behavior by modifying the physiologic balance between mesolimbic and nigrostriatal dopaminergic systems. The other actions of apomorphine and piribedil upon aggression, ferocity, and motor activity are not always in parallel and depend probably on the fact that piribedil is less specific, affecting also noradrenergic, serotonergic, histaminergic, and/or cholinergic circuits. The usefulness of piribedil against some forms of human tremor and its low-intensity antiakinetic action probably result from this pattern of pharmacologic activity.