Gerard Leclerc

Postjunctional α-adrenoceptors

SummaryThe postsynaptic α-adrenoceptors in rat aorta and in pithed rat were investigated according to their sensitivity to nine α-adrenergic agonists and to the selective antagonists yohimbine (α2) and prazosin (α1) and the non-selective one, phentolamine. In addition, in radioligand binding studies, the affinity and selectivity of the drugs were determined on rat cerebral cortex using [3H] yohimbine and [3H] prazosin.On rat aorta, prazosin is 1,000 times more potent than yohimbine against each α-adrenoceptor agonist, whether α1- or α2-selective. Rat aorta probably contains only α1-adrenoceptors.Pressor effects in pithed rats are mediated by post-junctional α1- and α2-adrenoceptors. The dose-response curve for α-methylnorepinephrine in the presence of prazosin, using Hofstees plots, revealed α1- and α2-adrenoceptors, respective proportions being 80.5 and 19.5%The postsynaptic alpha-adrenoceptors in rat aorta and in pithed rat were investigated according to their sensitivity to nine alpha-adrenergic agonists and to the selective antagonists yohimbine (alpha 2) and prazosin (alpha 1) and the nonselective one, phentolamine. In addition, in radioligand binding studies, the affinity and selectivity of the drugs were determined on rat cerebral cortex using [3H] yohimbine and [3H] prazosin. On rat aorta, prazosin is 1,000 times more potent than yohimbine against each alpha-adrenoceptor agonist, whether alpha 1- or alpha 2-selective. Rat aorta probably contains only alpha 1-adrenoceptors. Pressor effects in pithed rats are mediated by post-junctional alpha 1- and alpha 2-adrenoceptors. The dose-response curve for alpha-methylnorepinephrine in the presence of prazosin, using Hofstees plots, revealed alpha 1- and alpha 2-adrenoceptors, respective proportions being 80.5 and 19.5%.

Selective reduction of aromatic/aliphatic nitro groups by sodium sulfide

Abstract Sodium sulfide can be used to reduce selectively aromatic / aliphatic nitro groups. In the absence of water, the aromatic nitro group can be reduced selectively in the presence of a secondary aliphatic one. However, in the presence of a tertiary aliphatic nitro group, the reduction is accompanied by 50% of the styrene derivative 6 .

The use of lithium borohydride for deprotecting acetylated alcohols and phenols in the presence of N-acetylated guanidines

Abstract The behaviour of LiBH 4 and NaBH 4 on various O- and N-acetylated guanidines has been investigated.

Study of two alkylating derivatives: The p-isothiocyanato- and the p-methylisothiocyanato-clonidine

Pharmacological experiments with isolated rat aorta and radioligand binding studies in rat cerebral membranes were performed with the p-isothiocyanato (p-NCS) and p-methylisothiocyanato (p-CH2-NCS) derivatives of clonidine in order to assess their selectivity for alpha 1- and alpha 2-adrenoceptors, and to characterize their ability to alkylate alpha-adrenoceptors. Preincubation of rat aortic strips with both derivatives produced non-parallel rightward shifts in the dose-response curves of noradrenaline and significantly depressed the maximum response in a manner characteristic of irreversible receptor antagonists. The p-CH2-NCS derivative was slightly more potent than the p-NCS derivative. Further analysis of the data indicated that treatment of rat aorta with a 30 microM concentration of the p-CH2-NCS derivative alkylated all but 2.4 percent of the alpha-adrenoceptors, whereas a 100 microM concentration of the p-NCS derivative was required to produce a similar degree of alpha-adrenoceptor alkylation. Radioligand binding studies indicate an apparent 2 fold alpha2-adrenoceptor selectivity for the p-NCS derivative. In contrast, the p-CH2-NCS derivative displayed 7 fold selectivity for alpha 1-adrenoceptors. Interestingly, both alkylating derivatives of clonidine produced dose-dependent contractile responses in rat aorta with pD2 values of 6.30 and 5.56 for the p-NCS and p-CH2-NCS derivatives, respectively, relative to a pD2 of 7.67 for clonidine. The order of potency of the two alkylating derivatives of clonidine for producing contraction of rat aorta is the opposite of that for antagonizing the contractile effects of noradrenaline. The results suggest that the p-NCS and p-CH2-NCS derivatives of clonidine non-competitively antagonize noradrenaline by irreversibly alkylating alpha-adrenoceptors.

The reaction of amines with phthalimide derivatives a convenient synthesis of isoxazolidine

Abstract The reaction of tert-butylamine, isoxazolidine and hydrazine with N-[(3-chloropropyl)oxy]phthalimide is investigated. A convenient synthesis of oxazolidine is described.