Marco Cecchi

Inhibition of cortical acetylcholine release and cognitive performance by histamine H3 receptor activation in rats.

1 The effects of histamine and agents acting at histamine receptors on spontaneous and 100 mM K+‐evoked release of acetylcholine, measured by microdialysis from the cortex of freely moving rats, and on cognitive tests are described. 2 Local administration of histamine (0.1–100 μm) failed to affect spontaneous but inhibited 100 mM K+‐stimulated release of acetylcholine up to about 50%. The H3 receptor agonists (R)‐α‐methylhistamine (RAMH) (0.1–10 μm), imetit (0.01–10 μm) and immepip (0.01–10 μm) mimicked the effect of histamine. 3 Neither 2‐thiazolylethylamine (TEA), an agonist showing some selectivity for H1 receptors, nor the H2 receptor agonist, dimaprit, modified 100 mM K+‐evoked release of acetylcholine. 4 The inhibitory effect of 100 μm histamine was completely prevented by the highly selective histamine H3 receptor antagonist, clobenpropit but was resistant to antagonism by triprolidine and cimetidine, antagonists at histamine H1 and H2 but not H3 receptors. 5 The H3 receptor‐induced inhibition of K+‐evoked release of acetylcholine was fully sensitive to tetrodotoxin (TTX). 6 The effects of intraperitoneal (i.p.) injection of imetit (5 mg kg−1) and RAMH (5 mg kg−1) were tested on acetylcholine release and short term memory paradigms. Both drugs reduced 100 mM K+‐evoked release of cortical acetylcholine, and impaired object recognition and a passive avoidance response. 7 These observations provide the first evidence of a regulatory role of histamine H3 receptors on cortical acetylcholine release in vivo. Moreover, they suggest a role for histamine in learning and memory and may have implications for the treatment of degenerative disorders associated with impaired cholinergic function.

Cortical acetylcholine release elicited by stimulation of histamine H1 receptors in the nucleus basalis magnocellularis: a dual‐probe microdialysis study in the freely moving rat

Perfusion of the nucleus basalis magnocellularis (NBM) with histamine agonists and antagonists modulates the spontaneous release of cortical acetylcholine (ACh) in freely moving rats. Perfusion of the NBM with Ringer solution containing 100 mm K+ strongly stimulated the spontaneous release of cortical ACh in freely moving rats, whereas perfusion with 1 µm tetrodotoxin reduced cortical ACh spontaneous release by more than 50%. Administration of histamine to the NBM concentration‐dependently increased the spontaneous release of cortical ACh. Administration of H1 (methylhistaprodifen) but not H2 (dimaprit) or H3 (R‐α‐methylhistamine) receptor agonists to the NBM mimicked the effect of histamine. Perfusion of the NBM with either H1 (mepyramine or triprolidine) or H2 (cimetidine) receptor antagonists failed to alter ACh spontaneous release from the cortex, however, H1 but not H2 receptor antagonists antagonized the releases of cortical ACh elicited by histamine and methylhistaprodifen. Local administration of H3 receptor antagonists (clobenpropit and thioperamide) to the NBM increased the spontaneous release of ACh from the cortex; this effect was antagonized by H1 receptor antagonism. Conversely local administration of MK‐801, a noncompetitive receptor antagonist of the N‐methyl‐d‐aspartate receptor, to the NBM failed to alter ACh spontaneous release from the cortex and to antagonize ACh release elicited by histamine. This study demonstrates that activation of histamine H1 receptors in the NBM increases ACh spontaneous release from the cortex.

GABAergic mechanism in histamine H3 receptor inhibition of K+-evoked release of acetylcholine from rat cortex in vivo

Autoradiographic studies have suggested that the presence of H3 receptors, initially detected as autoreceptors inhibiting histamine release [1], is not restricted to histaminergic neurons [2–4]. Accordingly, functional studies have shown that H3 receptors modulate the release of several neurotransmitters, including acetylcholine (ACh) in vitro [5], and in vivo [6]. The present study assessed the location of H 3 receptors modulating ACh release.

Study on direct benzoannelations of pyrrole and indole systems by domino reactions with 4,5-dicyanopyridazine

Abstract The title pyridazine 1 was found to undergo hetero Diels–Alder [4+2] cycloadditions on the C(2)–C(3) double bond of pyrrole and indole systems; spontaneous loss of nitrogen from the primary adducts, followed by oxidation processes, afforded the corresponding fully aromatic benzoannelated skeletons in modest and reasonable yields, respectively. Competitive attacks of the same systems at the strongly electrophilic C-4 carbon of 1 , leading to substitution products, were evidenced.

Histamine H3 receptor inhibition of K+-evoked release of acetylcholine from rat cortex in vivo

In the brain, H 3 receptors function predominantly as presynaptic inhibitory receptors. Indeed, their activation moderates the in vitro-release of tritiated histamine [1], serotonin [2], noradrenaline [3] and acetylcholine [4]. In vivo, a modulation of hippocampal acetylcholine release through H 2 receptors has been suggested [5]. We now report that histamine inhibits the release of acetylcholine from cortex of freely moving rats through H 3 receptors.

Increase of acetylcholine release from cortex of freely moving rats by administration of histamine into the nucleus basalis magnocellularis.

Through the activation of cortical histamine H 3 receptors, histamine has been shown to inhibit acetylcholine release from rat cortex in vivo [1]. This effect is indirect, mediated by cortical GABA interneurons [2]. However, cholinergic nucleus basalis magnocellularis (NBM) neurons, which provide cholinergic innervation to the cortex [3], are excited by histamine in vitro [4]. Thus, histaminergic neurons might also facilitate cortical cholinergic activity. This study investigated NBM histaminergic/cholinergic interactions in vivo in the rat.

Reactivity and Synthetic Applications of 4,5-Dicyanopyridazine: An Overview

Despite the poor reputation of electron-deficient pyridazines in intermolecular Hetero Diels-Alder (HDA) reactions, 4,5-dicyanopyridazine (DCP) showed a surprising reactivity as a heterocyclic azadiene in inverse electron-demand HDA processes with different dienophiles. The use of alkenes, alkynes and enamines as 2π electron counterparts afforded dicyanocyclohexa-1,3-dienes and substituted phthalonitriles, respectively, while the use of suitable bis-dienophiles provides a general strategy for the one-pot synthesis of polycyclic carbo- and hetero-cage systems through pericyclic three-step homodomino processes. HDA reactions with heterocyclic dienophiles allowed direct benzoannelation: in particular, pyrrole and indole derivatives were converted to dicyano-indoles and -carbazoles. In addition an unprecedented reactivity of DCP as a very reactive heterocyclic electrophile at the C-4 carbon was also evidenced: by changing the experimental conditions, cyanopyrrolyl- and cyanoindolyl-pyridazines were obtained through reactions of pyrrole and indole systems as carbon nucleophiles in formal SNAr2 processes where a CN group of DCP acts as leaving group. Thus, careful control of the reaction conditions allows exploitation of both pathways for the synthesis of different classes of heterocyclic derivatives.

Adaptive Scheduling Algorithms for Multimedia Traffic in Wireless OFDMA Systems

This paper deals with the problem of finding an optimal subcarrier allocation strategy for uplink and downlink communications in an OFDMA metropolitan wireless system. In particular a two steps approach is considered; at the first step the scheduler establishes the amount of resources to assign to users on the basis of their quality of service (QoS) constraints, while, at the second step, channel conditions are used to allocate subcarriers to users. A simple strategy for choosing the appropriate modulation and coding scheme according to the channel conditions of the assigned subcarriers is also proposed.