Synthesis and hypolipidemic activity of new substituted (benzofuran-2-yl)-phenyl-carbinols.

The synthesis and pharmacological screening of a series of compounds structurally related to chloridarol was performed to discover new drugs for the control of hypercholesterolemia, a major risk factor for CHD

Effect of adenosine receptor modulation on pentylenetetrazole-induced seizures in rats

1. The effects of adenosine, the adenosine analogue, 2-chloroadenosine (2-CADO), the specific adenosine A(1) receptor agonist, N(6)-cyclopentyladenosine (CPA) and A(2) receptor agonist 5′-(N-cyclopropyl) carboxamidoadenosine (CPCA), were examined against seizures induced by acute administration of pentylenetetrazole (PTZ), 60 mg kg(−1), and PTZ kindled seizures, in rats. 2. Adenosine 1000 mg kg(−1), i.p., 5 min pretreatment and CPA 10 mg kg(−1) i.p., 60 min pretreatment, showed significant protection against acute PTZ-induced seizures while, CPCA up to 10 mg kg(−1) was ineffective. The adenosine analogue 2-CADO in a dose of 5 mg kg(−1) was only partially protective and on increasing the dose to 10 mg kg(−1), this protection was lost. 3. Theophylline, a non specific adenosine receptor antagonist at 50 mg kg(−1) and the specific adenosine A(1) receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), at 1 mg kg(−1), if administered before the maximally protective doses of adenosine and CPA, completely reversed the protection afforded by them against PTZ seizures. While, pretreatment with the adenosine A(2) receptor antagonist, 3,7-dimethyl-1-propargylxanthine (DMPX), failed to reverse the protection. 4. Adenosine and the adenosine A(1) receptor agonist in doses that protected against seizures after acute PTZ administration, offered only incomplete protection when tested against PTZ kindled seizures. 5. The effects of adenosine and adenosine receptor agonists on mean arterial pressure, heart rate and rectal temperature were studied, to rule out the possibility of their systemic effects mediating the protection of PTZ seizures. All these agents produced a fall in mean arterial pressure, heart rate and hypothermia in the doses exhibiting an anticonvulsant response. While the effect on blood pressure and heart rate was immediate i.e. seen within 5 min and, maintained throughout the observation period, the development of hypothermia lagged behind the onset of hypotension and bradycardia. However, there was no correlation between haemodynamic and hypothermic response and the anticonvulsant effect. 6. The results indicate that the adenosine mediated anticonvulsant effect is via stimulation of A(1) receptors. Hypotension and hypothermia do not appear to contribute to the protection observed with adenosine and the adenosine A(1) receptor agonists

Role of tachykinin NK receptors on the local and remote injuries following ischaemia and reperfusion of the superior mesenteric artery in the rat

1. Neuropeptides acting on tachykinin NK receptors play an important role in the amplification of inflammatory responses. We have assessed the effects of tachykinin NK receptor blockade on the injuries following intestinal ischaemia and reperfusion (I/R) in rats. 2. The tachykinin NK(1) receptor antagonist SR140333 dose-dependently (0.05 to 0.5 mg kg(−1)) suppressed the local (intestine) and remote (lung) increases in vascular permeability and neutrophil recruitment following mild I/R injury. A structurally-distinct NK(1) receptor antagonist, CP99,994, but not tachykinin NK(2) or NK(3) receptor antagonists also suppressed mild I/R injury. 3. Neonatal pretreatment with capsaicin effectively depleted sensory neurons and abrogated the injuries following mild I/R. 4. Treatment with SR140333 (0.5 mg kg(−1)) significantly reversed severe reperfusion-induced local and remote increases in vascular permeability, neutrophil recruitment, intestinal haemorrhage and blood neutropaenia, but did not prevent the lethality associated with severe I/R. 5. Post-ischaemic treatment with SR140333 significantly inhibited the elevations of TNF-α in the intestine and lung, but not serum, following severe I/R. The increase in the concentrations of IL-10 in the lung and serum were also suppressed. 6. Post-ischaemic blockade of tachykinin NK(1) receptors markedly inhibited the local and remote injuries, but not lethality, following reperfusion of the SMA in rats. Neuropeptides, possibly substance P, released from sensory nerves appear to account for the activation of these tachykinin NK(1) receptors. Antagonists of the tachykinin NK(1) receptor may be useful adjuncts in the treatment of the injuries which occur following reperfusion of an ischaemic vascular territory