Effects of the antimigraine compound zolmitriptan ('Zomig') on psychomotor performance alone and in combination with diazepam in healthy volunteers

Zolmitriptan (Zomig^TM) is a 5HT_1B/1D agonist which has the ability to cross the intact blood-brain barrier to access central as well as peripheral receptors. Because of the potential for central nervous system side effects, this randomized, double-blind, placebo-controlled, 6-period crossover study evaluated the effects of 2.5 and 5 mg doses of zolmitriptan on psychomotor performance and investigated any pharmacodynamic or pharmacokinetic interaction with diazepam. Twelve healthy volunteers received the following "treatments" as single doses: zolmitriptan 2.5 mg, zolmitriptan 5 mg, diazepam 10 mg, zolmitriptan 2.5 mg+diazepam 10 mg, zolmitriptan 5 mg+diazepam 10 mg and placebo. Pre-dose and at 1, 4, 8, and 24 h post-dose, the following validated battery of psychomotor tests was performed: Bond-Lader visual analogue scales (calmness, contentedness, and alertness factors), critical flicker fusion test, choice reaction time (recognition, motor, and total reaction times), finger-tapping test, number cancellation test and digit symbol substitution test. Plasma concentrations of zolmitriptan, its active metabolite, and diazepam and its active metabolites were measured at the same timepoints. Zolmitriptan 2.5 and 5 mg had no effect on psychomotor function when given alone. In contrast, diazepam 10 mg had profound effects, consistent with its sedative properties, but there was no synergism on concomitant administration of either dose of zolmitriptan. Plasma concentrations of zolmitriptan, diazepam, and their respective active metabolites were similar when the two drugs were given alone or in combination.     

Opioid modulation of LHRH release in vitro depends upon levels of testosterone in vivo

The in vitro release of LHRH from hypothalami of adult male rats (intact, 5-day castrates, 5-day castrates replaced with various doses of testosterone) was measured under basal conditions and after the addition of KCl, the opiate antagonist naloxone or the opiate agonist DAGO to the perifusion medium. Hypothalami from all treatment groups responded to 56 mM KCl with an increased output of LHRH. LHRH release was also induced by naloxone (10(-6)M), but only from tissues derived from intacts and castrates given physiological doses of testosterone. The opiate agonist DAGO (10(-6)M) did not alter the basal release of LHRH; it, however, caused a significant decrease in the K+-induced release of LHRH from hypothalami derived from intact rats and rats replaced with physiological levels of testosterone but not from those derived from castrate rats or castrate rats replaced with small amounts of testosterone. The specificity of this latter response was shown by its reversibility with naloxone. The lack of DAGO effects upon tissues from rats with low levels of steroid implied steroid dependency of the response to opioidergic influences and indeed, the response to DAGO was restored when testosterone was replaced at physiological doses. Measurement of hypothalamic LHRH content showed no significant differences between tissues obtained from intact, castrate and testosterone-replaced castrate rats. These in vitro data support the view that the inhibitory influence of opioids upon LHRH release depends on the presence of gonadal steroids in vivo.     

Peripheral facial paralysis in Petropolis]

The author presents 83 cases of "a frigore" peripheral facial palsy, occurred in the mountain city of Petropolis which has characteristics such as a tropical climate without any traces of a dry season and an average temperature of 50 degrees F to 73.5 degrees F. The author relates them with virus infections which appear within a year period. Fifty six patients belong to his clinic and have a follow up, while other 25 patients proceed from another clinics and from them he only has reports on sex, age, side of palsy and the beginning of illness. He shows that the largest number of cases occurred along the months of May, August, September and October. Season distribution for southern hemisphere is analysed. He also considers etiology, incidence, prevalence, treatment and results on patients studied.     

Neurosurgical anatomy of the anterior interhemispheric approach for aneurysms of the anterior communicating artery (26.6.92)

Summary The anterior interhemispheric approach for aneurysms of the anterior communicating artery was studied in ten cadavers. This approach presents several advantages over the pterional approach widely used in neurosurgery. It allows direct access to the region of the anterior communicating artery complex with minimal retraction of the brain and preservatioin of the olfactory tract and the gyrus rectus.

---

Bases anatomiques de l'abord inter-hémisphérique antérieur lors de la chirurgie des anévrysmes de l'artère communicante antérieure

Résumé Ce travail concerne l'abord neurochirurgical des anévrysmes de l'artére communicante antérieure par voie frontale interhémisphérique. L'étude anatomique a été réalisée sur dix sujets. Cette exposition possède de nombreux avantages comparée à la voie ptérionale habituelle : voie d'abord reduite médiane permettant une visualisation directe et symétrique du complexe artériel de l'artére communicante antérieure ; avec le moindre manipulation et retraction du cerveau en respectant les voies olfactives et le gyrus rectus.

     

Effect of histamine,acetylcholine and compound 48/80 on bronchoconstriction and release of eicosanoids in the dog

The effects of Hi and ACH aerosol and of intravenous infusion of compound 48/80 on bronchoconstriction and plasma levels of Hi, TXB₂, KH₂PGF₂ and KH₂PGE₂ were investigated in 11 bastard dogs. Administration of Hi and ACH aerosol induced bronchoconstriction accompanied by an increase in the plasma levels of Hi and TXB₂. No effect on the plasma levels of KH₂PGF₂ and KH₂PGE₂ was detected. Release of endogenous Hi by compound 48/80 induced bronchoconstriction and significant increases in the plasma levels of TXB₂ as well as of KH₂PGF₂ and KH₂PGE₂. The effects of a second administration of Hi and ACH aerosols after compound 48/80 did not differ qualitatively from the effects of the first aerosol administration. However, quantitatively, the second Hi aerosol induced significantly less bronchoconstriction and TXB₂ release. Similarly, effects of the second ACH aerosol tended to be decreased as compared to the first ACH aerosol, although the difference was not significant. The diminished effect of the agonists could be due to receptor desensibilization and/or release of adrenaline, which in turn decreases bronchoconstriction and eicosanoid release.