metiamide and Body-Weight

The effect of prolonged metiamide administration on serum gastrin, gastrin content of the antrum and gastric corpus, and G-cell population was studied in the rat. A single subcutaneous injection of metiamide (200 mg/kg) at the onset of 16 days of continous treatment with three daily injections was followed by a fivefold increase in serum gastrin level at 4 hr in fasted and at 4 and 6 hr in fed rats. After 16 days of metiamide, the fed rats showed a peak in serum gastrin level of the same magnitude as on day 1, but only at 4 hr. Two hours later, the levels decreased rapidly to basal values. In the fasted animals, the response to metiamide was reduced to a threefold increase at 2 hr. There was no difference in gastrin content of the antrum and gastric corpus nor in volume density of the G-cells after the prolonged treatment compared with the controls. It is concluded that in spite of rises in serum gastrin, prolonged metiamide medication has no effect on the gastrin content of the antrum and gastric corpus nor on the G-cell population in the rat. Furthermore, after prolonged treatment, metiamide-induced gastrin release is diminished.

Topics: Animals; Body Weight; Cell Count; Fasting; Gastric Mucosa; Gastrins; Male; Metiamide; Organ Size; Pyloric Antrum; Rats; Stomach; Thiourea

The effects of L-histidine, and of the specific histamine receptor agonists 2-methylhistamine and 4-methylhistamine, on the expression of morphine tolerance and physical dependence have been studied in mice. These agents were administered during the "withdrawal" phase of development. All of them significantly increased tolerance but reduced the degree of physical dependence. The effects of 2-methylhistamine, which has predominantly H1-receptor activity, were completely abolished by the prior administration of the H1-antagonist mepyramine. The H2-antagonist metiamide, on the other hand, did not alter the action of 2-methylhistamine on physical dependence, though tolerance was restored to its original level. The effects of 4-methylhistamine, which is a specific H2-receptor agonist, were inhibited by metiamide, but mepyramine was unable to reverse the actions of this agonist. The effects of L-histidine, the major precursor of brain histamine, were unaltered by mepyramine, but partially inhibited by metiamide. These experimental findings are discussed in detail, and are considered to give further support to the view that histamine is implicated in some way in the mechanisms of the "withdrawal" phase of morphine tolerance and physical dependence in mice, with H2-receptors probably playing the more important role.

Topics: Animals; Body Weight; Drug Interactions; Drug Tolerance; Female; Histidine; Humans; Male; Metiamide; Mice; Mice, Inbred Strains; Morphine; Morphine Dependence; Pyrilamine; Reaction Time; Substance Withdrawal Syndrome