To avoid the main drawbacks of prolonged treatment with levodopa (involuntary movements and the "on-off" phenomenon), we administered apomorphine by mouth to 14 patients with Parkinson's disease. This treatment caused azotemia, which we circumvented by switching to N-propylnoraporpine, whose nephrotoxic dose (80 mg six times per day) was larger than its therapeutic dose (10 to 15 mg six times per day). Slowly increasing doses induced significant improvement (P less than 0.005) in all 24 patients studied, transitory mental aberrations in seven, and release of growth hormone in three patients tested. In patients previously on prolonged levodopa administration, the dyskinesia and "on-off" phenomenon were almost identical with N-propylnoraporphine, but both drawbacks were reduced or abolished in six patients by coadministration of alpha-methyldopa hydrazine plus levodopa. This coadministration seemed to abolish tachyphylaxis. We conclude that N-propylnoraporphine is very useful in the treatment of Parkinson's disease.

Abstract:Although the subtypes of serotonin 5-HT 1 receptors have distinct structure and pharmacology, it has not been clear if they also exhibit differences in coupling to cellular signals. We have sought to compare directly the coupling of 5-HT 1A and 5-HT 1B receptors to adenylyl cyclase and to the mitogen-activated protein kinase ERK2 (extracellular signal-regulated kinase-2). We found that 5-HT 1B receptors couple better to activation of ERK2 and inhibition of adenylyl cyclase than do 5-HT 1A receptors. 5-HT stimulated a maximal fourfold increase in ERK2 activity in nontransfected cells that express endogenous 5-HT 1B receptors at a very low density and a maximal 13-fold increase in transfected cells expressing 230 fmol of 5-HT 1B receptor/mg of membrane protein. In contrast, activation of 5-HT 1A receptors stimulated only a 2.8-fold maximal activation of ERK2 in transfected cells expressing receptors at 300 fmol/mg of membrane protein but did stimulate a 12-fold increase in activity in cells expressing receptors at 3,000 fmol/mg of membrane protein. Similarly, 5-HT 1A , but not 5-HT 1B , receptors were found to cause significant inhibition of forskolin-stimulated cyclic AMP accumulation only when expressed at high densities. These findings demonstrate that although both 5-HT 1A and 5-HT 1B receptors have been shown to couple to G proteins of the G i class, they exhibit differences in coupling to ERK2 and adenylyl cyclase. Key Words: Extracellular signal-regulated kinase-2-Mitogen-activated protein kinase -Cyclic AMP-5-HT 1A receptors-5-HT 1B receptors-Serotonin.

The authors report experiments in rats with 6-hydroxydopamine (6-OHDA), a chemical agent used for creating lesions in catecholamine neurons. Stereotaxic injection of 6-OHDA into the compact zone of the substantia nigra induced degeneration of the nigrostriatal dopamine (DA) system, confirmed by histology and histochemistry of the substantia nigra and by dopamine determinations in the neostriatum. These observations closely mimic those found in Parkinson's disease. In the experimental model a rotatory behavior is induced by DA agonists; this response has been used to test drugs for potential therapeutic use and also in basic studies of the extrapyramidal system. This technique may be useful in developing other experimental models for neurosurgical problems involving catecholamine pathways.

We evaluated the fractures of the lumbar and sacral vertebral limbus by disc impingement at the peripheral ring apophysis in 23 adults associated with trauma in 16 of them. Lumbalgia, radicular pain and narrow canal symptoms are the presenting forms of this underdiagnosed pathology. CT is the best method of examination, while plain roentgenograms and MR are usually negative. Accurate diagnosis and surgical technique with larger exposure are needed to resect the fractured fragments and protruded disc material for decompressing the roots and the dural sac. Our results were very good on the majority of cases.

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