A new series of 6-chloro-2,3-dihydro-4(1H)-quinazolinone derivatives as antiemetic and gastrointestinal motility enhancing agents.

New 6-chloro-2,3-dihydro-4(1H)-quinazolinones (24-27) have been synthesized and evaluated for gastrointestinal prokinetic and antiemetic activities in comparison with structurally related benzamides (21-22) and 6-chloro-2,3-dihydro-(1H)-1,3-benzoxazolin-4-ones (28). Their key pharmacophoric element has been defined as a 6-membered ring replacing the "virtual ring" arising from the hydrogen bond between amidic nitrogen and methoxy group in metoclopramide (1) and structurally related benzamides (2-10). Variations of heterocycle linking groups have pointed out that a lipophilic aromatic group in position 1 plays an important role for pharmacological properties, while the steric restriction and the modification of the side-chain nucleophilicity are uneffective both for the in vitro and in vivo activity. Some of these compounds very effectively enhance gut peristaltic activity in vitro (rabbit jejunum), increase gastric emptying of a semisolid meal (in rats), and inhibit cisplatin-induced emesis (in pigeons), favourably comparing with cisapride.

Polymodal dose-response curve for oxytocin in the social recognition test.

Available data concerning the effect of oxytocin on memory are often inconsistent. In the present study it was found that oxytocin, intracerebroventricularly injected to adult male rats in a dose range of 1 fg-10 ng/rat immediately after a 5-minute encounter with a juvenile, significantly reduces the social investigation time of the adult rat towards the same juvenile during a second encounter (120 min later) with two peaks of activity, at 10 fg and 1 ng/rat. Larger doses of oxytocin were ineffective. The oxytocin antagonist d(CH2)5Tyr(Me)-Orn8-vasotocin, injected 5 min before oxytocin by the same route and at the same doses, while being ineffective per se, completely abolished the memory-improving effect of a low dose of oxytocin (1 ng/rat) and, on the other hand, turned into memory-improving the effect of a high dose of oxytocin (500 ng/rat).

Galantide stimulates sexual behaviour in male rats.

While intracerebroventricular injection of galanin (5 micrograms/rat) inhibited sexual behavior in experienced male rats--without producing any other locomotor or behavioral deficit-, injection of the galanin antagonist, galantide, by the same route (1 or 2 micrograms/rat) stimulated sexual behavior (improving arousal, motivation and performance indexes) and antagonized the effect of galanin. These data further suggest that galanin plays a physiological role in male sexual behavior.

Male sexual behaviour: further studies on the role of alpha 2-adrenoceptors.

The role of central alpha 2-adrenoceptors in male sexual behaviour was investigated by administering the selective agonist, guanabenz, and the selective antagonist, efaroxan, to both sexually experienced and sexually inexperienced male rats. In sexually experienced animals, guanabenz, at the dose of 1 mg/kg i.p., increased mount and intromission latencies (ML, IL), intercopulatory interval (ICI) and post-ejaculation interval (PEI), and reduced mount and intromission frequencies (MF, IF) and copulatory efficacy (CE). Efaroxan, at the dose of 10 mg/kg i.p., reduced ML and IL. In sexually inexperienced animals, guanabenz, at the dose of 1 mg/kg i.p., slightly reduced the percent of animals achieving ejaculation and increased PEI. Efaroxan, either at the dose of 3 or 10 mg/kg i.p., increased the percent of animals achieving ejaculation and--only at the dose of 10 mg/kg i.p.--reduced EL. Finally, in sexually experienced animals, efaroxan (10 mg/kg i.p.) prevented the effect of guanabenz (1 mg/kg i.p.). On the whole, these data further indicate that, in rats, male sexual behaviour is positively modulated by brain noradrenergic systems.

[Drug-induced changes in the teeth and mouth. II]. / Alterazioni odontostomatologiche da farmaci. Nota II.

As in the previous paper the unwanted effects of drugs or chemicals in the orofacial region are described. The authors take into consideration alterations such as gingival hyperplasia and hypertrophy, discoloration of the oral mucosa and teeth, oral ulceration and stomatitis, cervical lymphadenopathy, drug induced blood dyscrasias, bleeding caused by aspirin and other drugs, and cleft lip and cleft palate.

[Odontostomatological changes induced by drugs. I]. / Alterazioni odontostomatologiche da farmaci. Nota I.

The purpose of the present review is to describe the unwanted effects of drugs or chemicals in the orofacial region. The authors take into consideration the alterations of salivation such as xerostomia and ptyalism, disturbances of sense of taste, halitosis and pain and swelling of the salivary glands. The dental surgeon who suspects that an oral alteration might be a drug reaction can play an important role in preventing the development of more severe toxic effects. All this points to the importance of the knowledge of pharmacology for dental practitioners.