Synthesis and cardiovascular properties of fluorenyl derivatives related to verapamil

A series of fluorenyl analogues of verapamil were synthesized and their cardiovascular properties on guinea pig isolated atria and isolated perfused heart evaluated. The compounds were also tested for their calcium antagonistic activity on guinea pig aorta. They were found to be poor calcium antagonists, but showed negative inotropic and antiarrhythmic properties. The results obtained seem to indicate that their mechanism of action differs from that of verapamil

Antinociceptive Effect of R-(+)-Hyoscyamine on the Conjunctival Reflex Test in Rabbits

R-(+)-Hyoscyamine (1-10 microg/kg, s.c.) dose-dependently increased the local anesthetic effect of procaine (50 microg/ml) and lidocaine (50 microg/ml) in the conjunctival reflex test in the rabbit. This potentiating effect is completely prevented by the M1 antagonist dicyclomine (10 mg/kg, s.c.). The intensity of R-(+)-hyoscyamine antinociception was comparable to that induced by morphine (2 mg/kg, s.c.) and minaprine (15 mg/kg, s.c.), used as analgesic reference drugs. In the same experimental conditions, the S-(-)-enantiomer of atropine (0.1-10 microg/kg, s.c.), was completely ineffective. The present results confirm the ability of R-(+)-hyoscyamine to produce a paradoxical antinociceptive effect mediated by a cholinergic mechanism not only in rodents but also in the rabbit

Docking analyses on human muscarinic receptors : unveiling the subtypes peculiarities in agonists binding

The study presents a docking analysis for the interaction capabilities of some muscarinic receptors (i.e., M(1), M(2), and M(5)) whose full-length models were previously generated by us. In detail, the docking simulations involved a dataset of 30 agonists, taken from the literature, including a first series of oxathiolane/dioxolane congeners and a second subset of more heterogeneous ligands. The obtained results unveil that it is possible to discriminate among the binding modes of considered muscarinic receptors, developing specific interaction patterns which are significantly different for the arrangement of both polar and hydrophobic interactions. Thus, the M(1) subtype possesses the widest binding site, while the M(2) receptor is characterized by a large but asymmetric region that accommodates the ligand''s ammonium head and finally the M(5) binding site is quite similar to that of M(2) subtype being univocally characterized by a second aspartate residue which interacts with the ammonium head. The significant correlations between docking scores and affinity values afford an encouraging validation for the reported binding modes and confirm the key role of molecular flexibility in the ligand recognition of muscarinic receptors

Synthesis and pharmacological evaluation of some pyridyl cyclopropylmethylamines and their methiodides as nicotinic receptor ligands of hexahydro-[2]pyrindine derivatives as conformationally restricted analogs of the nicotinic ligands

In this paper the synthesis of novel nicotinic ligands were studied. In addition was also evaluated the affinity values expressed as the concentration of the ligand able to displace from the receptor site the 50% of the radioligand

Synthesis of hexahydro-[2]pyrindine derivatives as conformationally restricted enalogs of the nicotinic ligands arecolone and isoarecolone

Synthesis of pyrindine derivatives as analogs of the arecolone and isoarecolone were performed. In addition binding parameters such as affinity and selectivity were investigated

Reduced flexibility hybrids of the nicotinic agonists 1,1 dimethyl-4-acetylpiperazinium iodide and 2-(dimethylamino)methyl-5-methyl-cyclopentanone methiodide

--