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The enantiomers of a number of catecholamines, including (alpha S)- and (alpha R)-erythro-alpha-methylepinephrine, were evaluated for their capacity to compete for binding sites in rat forebrain homogenates with [3H]prazosin, a ligand which selectively binds to adrenergic receptors of the alpha 1 subtype. (alpha R)-erythro-alpha-Methylepinephrine is devoid of apparent biological activity, but the activity of the alpha S isomer is substantial. The latter is less active than the endogeneous catecholamines, (R)-norepinephrine and (R)-epinephrine, but the stereospecific competition for [3H]prazosin binding sites by the catecholamine isomers with the beta R configuration is additional evidence that (alpha S)-erythro-alpha-methylepinephrine may be a biologically active metabolite of L-alpha-methyl-3,4-dihydroxyphenylalanine.

Sterically hindered 5,11-dicarbo analogues of clozapine were prepared as potential chiral antipsychotic agents, with the possibility that for a particular analogue the antipsychotic activity of clozapine may reside in one enantiomer of the analogue whereas other unwanted biological effects of clozapine may be caused by the other enantiomer. Variable-temperature proton nuclear magnetic resonance studies showed that although 5-methylene-10-(4-methylpiperazino)-5H-dibenzo[a,d]cycloheptene exists at room temperature as configurational enantiomers, the activation energy for thermal racemization is 19 kcal mol-1 at 105 degrees C, and it is doubtful that the enantiomers of this analogue can be isolated under usual laboratory conditions. The (Z)-5-ethylidene and 5-isopropylidene analogues have activation energies greater than 23 kcal mol-1 at 160 degrees C, and thus there is a possibility that the analogues can be obtained as their respective enantiomers. 5-Methyl-10-(4-methylpiperazino)-5H-dibenzo[a,d]cycloheptene incorporates a chiral center which is not thermally racemized, but it exists at room temperature as two diasteromers with an activation energy for inversion of the 5H-dibenzo[a,d]cycloheptene ring of 21 kcal mol-1. When the 5,11-dicarbo analogues were tested in vitro for biological activity and their activities were compared to that of clozapine, the affinities for muscarinic and dopamine D-1 and D-2 sites were reduced but were still substantial. Thus the respective biological activities of the racemates indicate that the biological activities of the thermally stable enantiomers may be of importance in finding a clozapine derivative with fewer side effects than those shown by clozapine itself. Because of the susceptibility of the enamines to acid-catalyzed hydrolysis, resolution into respective enantiomers is not anticipated.

The capacity of a series of intraneuronal metabolites of L-alpha-methyldopa to compete for alpha-1 ([3H]prazosin, alpha-2([3H]clonidine and beta ([3H]dihydroalprenolol) receptor binding in rat forebrain was studied. Each metabolite studied had a unique order of activity at each receptor. These data show that (-)-erythro-alpha-methylnorepinephrine and (-)-erythro-alpha-methylepinephrine compete with high affinity for alpha-2 receptors, thereby supporting the suggestion that alpha-2 receptors mediate hypotensive effects of L-alpha-methyldopa . Furthermore, these metabolites of L-alpha-methyldopa competed with high potency for beta-1 receptors in forebrain and (-)-erythro-alpha-methylepinephrine was more potent than (-)-epinephrine, (-)-norepinephrine and (-)-erythro-alpha-methylnorepinephrine in competing for beta-2 receptors on human lymphocytes. These data suggest that beta receptor stimulation may be important in determining the net effects of L-alpha-methyldopa. L-alpha-Methyldopa metabolites were much less potent than (-)-epinephrine and (-)-norepinephrine in competition for alpha-1 receptors. (+/-)-alpha-Methyldopamine was less potent than other l-alpha-methyldopa metabolites at all three receptors, suggesting that it is unlikely to be an important hypotensive metabolite of L-alpha-methyldopa.

The microtubules associated with the pellicle, reservoir and locomotory flagellum of Euglena granulata were subjected to rotational analysis using the technique of Markham et al. The results indicate that the microtubules have 11-14 subunits when viewed in transverse section. Rotational analysis of the entire locomotory flagellum was also conducted to better demonstrate the nature of the arms extending from the peripheral microtubules.

Ampicillin and tetracycline, in doses of 2 g a day, were compared in the treatment of acute exacerbations of chronic bronchitis. Seventy-nine patients were followed for 3 to 29 months and were treated for 118 exacerbations. Clinical improvement occurred after 10 days of treatment with either drug in over 80% of the cases. Haemophilus influenzae and Diplococcus pneumoniae were eradicated from the sputum more than 60% of the time, but in general there was a poor correlation between bacteriological clearing and clinical response. The effect of chemoprophylaxis with ampicillin and tetracycline in doses of 1 g a day on the frequency of acute exacerbations of bronchitis was compared with that of a placebo. Seven hundred eighty prophylactic regimens, consisting of one capsule every 12 hr for 5 days beginning with the first sign of a cold, were prescribed for 76 patients. Irrespective of the regimen, an acute exacerbation of bronchitis was encountered at approximately 13% of the follow-up visits to the clinic.