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Biomedical subjects

M Orsetti

Publications and source records attributed to M Orsetti.

At least 37 records · Page 2Linked to original sources
PubMed1989

The effect of chronic atropine administration on mouse motility and on ACh levels in the central nervous system.

Changes in mouse motility and CNS cortical and subcortical ACh levels were studied after chronic (20 days) administration of 30, 40 and 60 mg/kg/day atropine. An increase in motility similar to that induced by acute atropine administration was observed, whereas the ACh levels reduction caused by acute administration was not repeated. These results suggest that changes in mouse motility caused by atropine are not correlated to its modification of ACh levels in the CNS.

Acetylcholine↗
PubMed1989

Potential histamine H2-receptor antagonists. Synthesis, structure and activity of a few open models related to classical H2-antagonists.

A few ethers and oximes structurally related to classical H2-antagonists have been synthetized and tested for their in vitro H2-antagonist activity. The compounds in which cyclic "urea equivalent" groups are joined to a cyclohexylmethyl moiety showed a high increase of activity in comparison with the unsubstituted analogues. This finding supports the hypothesis of the existence of an accessorial binding area on H2-receptor near the site fitted by cyclic "urea equivalent" groups.

Animals↗
PubMed1988

Histamine H2-receptor blocking activity of ranitidine and lamtidine analogues containing aminomethyl-substituted aliphatic systems.

The possibility that the aromatic component in the classical H2-antagonists might not be essential for histamine H2-receptor blockade has been investigated. In the ranitidine series the removal of the furan ring is accompanied by a drastic decrease in H2-blocking activity, but not by its disappearance (compound HB5:KB on guinea pig isolated atria 31.6 microM) whereas in the lamtidine analogues the substitution of the phenyl moiety with the more reduced pi-bonded CH3-C = N-area generates a compound whose activity is comparable to that of cimetidine (KB on atria 1.12 microM; ID50 in the lumen-perfused stomach of the anaesthetized rat 3.61 mumol/kg i.v.). The results also indicate that the diaminofurazan group confers high affinity at the histamine H2-receptor. It is concluded that the aromatic portion of H2-antagonists related to ranitidine and lamtidine is not a minimal requisite for activity when an appropriate polar group is used as an "urea equivalent" moiety.

Animals↗
PubMed1988

New ranitidine analogues containing the 2-aminobenzimidazole moiety: in vivo and in vitro histamine H2-receptor blocking activity.

The paper reports the pharmacological profile of a new series of ranitidine analogues in which the diaminonitroethene group is replaced by the 2-amino-5(6)-substituted and unsubstituted benzimidazole moieties. These derivatives show a histamine H2-receptor blocking activity comparable to that of the model both in vitro (KB on atria 0.16-1.15 microM) and in vivo (ID50 on the perfused stomach of the anaesthetized rat from 0.34 to 4.10 mumol kg-1 i.v.). The results are consistent with the hypothesis that, at least in the ranitidine analogues, the "urea equivalent" moiety may be replaced by a polar group partially ionized at physiological pH without loss of H2-blocking activity.

Animals↗
PubMed1988

Pharmacological profile of new histamine H2-receptor antagonists related to cimetidine, ranitidine and lamtidine.

New compounds structurally related to cimetidine, ranitidine and lamtidine have been prepared and tested for their histamine H2-receptor blocking activity on guinea-pig atria, rat perfused stomach and frog isolated gastric mucosa. These derivatives contain as a polar group, a diaminofurazan moiety, a 3-amino-4-methylfurazan or a 3-amino-4-phenylfurazan moiety. Ranitidine and lamtidine analogues display strong H2-antagonist activity in-vitro (KB on atria 0.037 microM and 0.0039 microM, respectively) and in-vivo on the lumen-perfused stomach of the anaesthetized rat (ID50 0.13 mumol kg-1 and 0.023 mumol kg-1 i.v., respectively). However, lamtidine analogues are ineffective in blocking the histamine-induced increase of H+ output in the frog isolated gastric mucosa. On the basis of the anomalous results in the frog, it is concluded that caution must be exercised in extrapolating information from amphibian to mammalian tissues with regard to the structure and the function of histamine receptors.

Animals↗
PubMed1987

Acetylcholine levels in the spinal cord after atropine, diisopropylfluorophosphate and naphthylvinylpyridine.

The decay of ACh levels from the death of the rat to longer time intervals has been estimated in the rat cervical spinal cord. The ACh levels at the beginning of the postmortal decay have been evaluated by extrapolation to t = 0 of the linear regressions log ACh concentrations vs time (t) from the rat decapitation. Atropine, diisopropylfluorophosphate (DFP) and naphthylvinylpyridine (NVP) caused a reduction of the ACh levels evaluated before the beginning of the postmortal decay. The levels of ACh at stabilization of the postmortal decay were increased by atropine and DFP. These effects may be correlated to modifications caused by the studied drugs on the ACh synthesis, release and destruction.

Acetylcholine↗
PubMed1986

Action of arecoline on the levels of acetylcholine, norepinephrine and dopamine in the mouse central nervous system.

Modifications caused by arecoline (2 mg/kg and 10 mg/kg injected subcutaneously) in the levels of acetylcholine (ACh), norepinephrine (NE) and dopamine (DA) in the mouse cortex and "subcortex" were studied. The animals were killed by microwave irradiation of the head 15 minutes after drug administration. Arecoline 10 mg/kg caused a reduction in levels of ACh in the cortex and "subcortex" at the limit of statistical significance (p 5-10%) and a statistically significant reduction in levels on NE. A statistically significant increase in DA was observed only in the cortex after 2 mg/kg and 10 mg/kg of arecoline.

Acetylcholine↗
PubMed1986

Action of a chronic administration of mescaline in dynamic behavioural situations.

The modifications of the rat behaviour caused by a chronic administration of mescaline were studied in two schedules of operant conditioning. In the "periodic conditioning" test, the schedule of reinforcement was changed from a fixed ratio to a fixed interval schedule. Mescaline (4 mg/kg/day and 10 mg/kg/day) caused no modification of the ability of the rat to adapt its behaviour to the new experimental situation. In the "reversal test" the contingency for food delivery was switched from one lever, where responses were previously reinforced to the other lever where responses had no programmed consequences. A chronic administration of mescaline (4 mg/kg/day) caused a total incapacity of the rat to switch to the lever which became reinforced in the reversal trial. A chronic administration of 9 mg/kg/day of mescaline had an excitatory effect and the number of reinforced responses in the II and III reversals exceeded the unreinforced responses in a measure greater than in the controls.

Animals↗
PubMed1986

Mescaline action on "memory decay" and "problem solving" behavior in the rat.

The modifications of behavior caused in the rat by a chronic oral administration of mescaline have been studied in three experimental situations. In the staircase maze mescaline accelerated the spontaneous decay on the conditioned reflex (memory decay) during the period without daily training. Only the results observed at 30 mg/kg/day of mescaline were statistically significant. In a T maze two lateral alleys closed by two swinging doors, 30 mg/kg/day of mescaline increased the time spent in opening the first door. When the two doors of the lateral alleys were closed with a latch, mescaline 30 mg/kg/day, caused an increase in the time spent by the rat in opening the doors. Mescaline caused an increase in food consumption. The increase at 30 mg/kg/day is statistically significant.

Administration, Oral↗
PubMed1986

Dose versus survival time curves in the evaluation of 'prompt' and 'delayed' acute toxicities.

The acute toxicity of arecoline, diisopropylfluorophosphate, nicotine and pilocarpine alone or in association with atropine has been evaluated from percentage lethality and from the linear correlation of (doses/(survival time] vs doses. The experimental points obtained with arecoline and diisopropylfluorophosphate, alone or in association with atropine 50 mg kg-1, are apparently ordered according to two straight lines. That at lower doses gave the LD50 values of the compounds studied. The values found are comparable to those found with percentage lethality. The straight line found at high doses may indicate that over certain doses the drugs kill by a different mechanism. It is concluded that the evaluation of the survival time may be a reliable method in identifying and in evaluating quantitatively the two forms of toxicity.

Animals↗