A wide variety of tissues undergo a change of functional state on exposure to noradrenaline or adrenaline. Those molecular constituents of the effector cells of a tissue with which molecules of these catecholamines must first interact in order to produce a change of state — or response — of the tissue, are the so-called adrenoceptors (also commonly called adrenergic receptors). For convenience, we refer to noradrenaline, adrenaline and other agents which produce responses in tissues by interacting with adrenoceptors, as adrenergic agonists. An agent which specifically inhibits a response produced by an adrenergic agonist is referred to as adrenergic blocking agent or adrenergic antagonist.

The Classification of Adrenoceptors (Adrenergic Receptors). An Evaluation from the Standpoint of Receptor Theory

The Methylation Effect in Medicinal Chemistry Eliezer J. Barreiro,* Arthur E. K€ummerle, and Carlos A. M. Fraga Laborat orio de Avaliac-~ao e Síntese de Subst̂ancias Bioativas (LASSBio), Faculdade de Farm acia, Universidade Federal do Rio de Janeiro, CCS, Cidade Universit aria, CP 68.006, 21941-902 Rio de Janeiro, RJ, Brazil Programa de P os-Graduac-~ao em Farmacologia e Química Medicinal, Instituto de Cîencias Biom edicas, Universidade Federal do Rio de Janeiro, Cidade Universit aria, Ilha do Fund~ao, Rio de Janeiro, RJ, Brazil Programa de P os-Graduac-~ao em Química, Instituto de Química, Universidade Federal do Rio de Janeiro, Cidade Universit aria, Ilha do Fund~ao, Rio de Janeiro, RJ, Brazil

The methylation effect in medicinal chemistry.

Suppression of firing activity of 5-HT neurons in the dorsal raphe by alpha-adrenoceptor antagonists

1 The effects of isoprenaline, propranolol and phentolamine, were studied on tritiated noradrenaline overflow elicited by postganglionic nerve stimulation in guinea-pig isolated atria. 2 Isoprenaline (1.2 times 10-minus 8M) increased while propranolol (1.0 times 10-minus 7M) reduced the overflow of tritiated noradrenaline evoked by nerve stimulation. These effects were less than those of phentolamine (3.1 times 10-minus 6M), which increased by approximately three-fold the overflow of [3H]-noradrenaline elicited by nerve stimulation. 3 Neuronal accumulation of tritiated noradrenaline in guinea-pig atria was not affected by isoprenaline, propranolol or phentolamine at the concentration employed in this study. 4 Isoprenaline (1.2 times 10-minus 8M) induced a positive chronotropic effect of about 80 percent of the maximum. On the other hand, propranolol produced a shift to the right in the frequency-response curve to nerve stimulation and in the concentration-response curve to exogenous noradrenaline in guinea-pig atria. 5 In the isolated nictitating membrane of the cat, the frequency-response curve to nerve stimulation was not modified by propranolol, while in the presence of 3.9 times 10-minus 6M of N,-2-(2,6-dimethylphenoxy)propyl-N,N,N-trimethylammonium (beta-methyl-TM 10) there was a shift to the right and a depression of slope. Neither propranolol nor beta-methyl-TM 10 affected responses to exogenous noradrenaline. 6. The effects of isoprenaline and of propranolol on transmitter release are compatible with the view that in addition to the presynaptic negative feed-back mechanism for noradrenaline release by nerve stimulation mediated via alpha-adrenoceptors a positive feed-back mechanism exists in adrenergic nerve endings which is triggered through the activation of presynaptic beta-adrenoceptors.

POSSIBLE ROLE OF A β‐ADRENOCEPTOR IN THE REGULATION OF NORADRENALINE RELEASE BY NERVE STIMULATION THROUGH A POSITIVE FEED‐BACK MECHANISM

Publisher Summary This chapter discusses the chemistry, production, applications, and health effects of chitin, chitosan, and co-products. Chitin and chitosan are weak bases, and have been tested to have material and biological properties that might be beneficial to enhance wound repair. Both of them have great influence on different stages of wound healing in the experimental animal models. Chitosan polymers can interact with and modulate the migration behavior of neutrophils and macrophages modifying subsequent repair process, such as fibroplastica and reepithelialization. Chitosan has many industrial, agricultural, pharmaceutical, and cosmetic applications. Safety and toxicological studies have been performed on chitosan to address issues related to its regulatory status. Based on its definition of functional foods, chitin and chitosans possess most of the required attributes related to enhancement of immunity, prevention of illness, delaying of aging, recovery for illness, and control of biorhythm. Thus, the use of chitosan in foods, such as potato chips, has been in commercial practice for some time. Therefore, regulatory status of chitosan varies from country to country and its use in food requires further studies to address issues of concern.

Chitin, Chitosan, and Co-Products: Chemistry, Production, Applications, and Health Effects

Steric Aspects of Adrenergic Drugs

The Easson-Stedman hypothesis that dextro isomers of sympathomimetic amines have pharmacologic activities similar to their corresponding desoxy derivatives was tested in the catecholamine-depleted (reserpine, 5 mg/kg i.p., 16-24 hr previously) rat vas deferens. Cumulative dose-response curves were obtained, in vitro, for D and L isomers of norepinephrine, epinephrine, cobefrin, metaraminol, phenylephrine, synephrine, octopamine, norephedrine and ephedrine and their corresponding desoxy derivatives, dopamine, epinine, α-methyldopamine, α-methyl- m -tyramine, m -tyramine, N-methyltyramine, tyramine, (+)-amphetamine and (+)-methamphetamine, respectively. All D(-) isomers retained their ability to produce a contraction and were more active than their L(+) isomers or desoxy derivatives. L(+)-Norepinephrine and L(+)- epinephrine are essentially directly-acting and their effects were equal to those of dopamine and epinine, respectively. All other L(+) isomers possess a considerable indirect component, as do their desoxy derivatives, and both groups produced essentially similar effects. The results suggest that the Easson-Stedman hypothesis holds true over a wide range of substances in the catecholamine-depleted preparation but not in the untreated preparation where the dose-response curves of indirectly-acting desoxy derivatives and L(+) isomers appear to be related to their known affinity for catecholamine uptake sites. Further classification of sympathomimetic amines is carried out.

Steric aspects of adrenergic drugs. II. Effects of DL isomers and desoxy derivatives on the reserpine-pretreated vas deferens.

In the article by P. N. Patil, J. B. LaPidus and A. Tye, Vol. 155, No. 1, January 1967, corrections should be made as follows: 1) In figure 2 the definitions for the symbols given on the figure itself are incorrect. The figure legend gives the correct definition for each curve. 2) In figure 8 the unidentified dose-response curve, ▴—▴, is that of the reference drug D(-)-norepinephrine.

Steric aspects of adrenergic drugs. i. comparative effects of dl isomers and desoxy derivatives

In the article by Popat N. Patil, A. Tye and J. B. LaPidus, Vol.148, No. 2, May 1965, in table 2 on page 161 and in table 3 on page 164 all the P values should read as . In the References, page 168, Schaumann, O. should read Schaumann, I.

A PHARMACOLOGiCAL STUDY OF THE EPHEDRINE ISOMERS

Combinations of meparfynol and anticonvulsant drugs were tested for anti-Metrazol® potency and neurotoxicity in mice. The addition of meparfynol to an anticonvulsant did not cause the protective index to rise above that of the better component in the combination.

A. Tye

Papers

Steric Aspects of Adrenergic Drugs

Steric aspects of adrenergic drugs. II. Effects of DL isomers and desoxy derivatives on the reserpine-pretreated vas deferens.

Steric aspects of adrenergic drugs. i. comparative effects of dl isomers and desoxy derivatives

A PHARMACOLOGiCAL STUDY OF THE EPHEDRINE ISOMERS

Anti‐metrazol® efficacy of combinations of meparfynol and anticonvulsant drugs