A randomised bouble-blind placebo controlled trial of lidamidine HCL in irritable vowel syndrome

BACKGROUND: We have previously shown electro-mechanical recto-anal alterations in irritable bowel syndrome patients (Awad R. Neurogastroenterol Motil 1993; 5; 265-271). To assess whether the alpha 2-agonist lidamidine HCL is able to modify these physiological alterations and alleviate clinical symptoms, 50 patients with irritable bowel syndrome were studied in a random, double blind, placebo-controlled trial. METHODS: Lidamidine HCL (4 mg) or placebo was taken orally t.i.d. with food. Fasting and post-prandial electrical and mechanical activities of rectum and internal anal sphincter were recorded before and at the end of treatment. Recto-anal sensitivity was also tested. RESULTS: After treatment, post-prandial duration of spontaneous recto-anal inhibitory reflex diminished in the lidamidine group (18.9 +/- 1 vs. 15.1 +/- 1.3 sec; p < 0.05). Amplitude of induced rectoanal inhibitory reflex decreased after lidamidine (24.6 +/- 2.9 vs 17.3 +/- 3 mmHg; p = 0.02). Rectal electrical activity showed no changes during basal and post-prandial periods in any group. Rectal painful sensation decreased after treatment with lidamidine (54.8 +/- 5.4 vs 43.6 +/- 3.5 ml; p < 0.05) as well as with placebo (p < 0.05). Abdominal distension and requency, severity and duration of pain diminished in both groups (p < 0.05). CONCLUSION: Lidamidine decreased the augmented mechanical response to food, reduced rectal sensitivity, and relieved symptoms. These facts suggest that in spite of the strong placebo response obtained, lidamidine HCL can become a useful alternative for treatment of patients with irritable bowel syndrome.

Antinociceptive effects of calcium channel blockers in the rat

1. The effects of cinnarizine and nifedipine on the nociceptive threshold and opiate antinociception were e evaluated by the rat rail-flick test. 2. male Wistar rats (390-410 g) treated with intraperitoneal (ip) or intrathecal (it) cinnarizine, but not with it nifedipine, displayed a dose-dependent antinociception. The estimated AD50 values of cinnarizine were 3.55 microng/Kg (coeficience limits, 1.99 to 6.32) and 125.9 microng/Kg (46.1 to 343.7) for the it and ip routs of administration, respectively. The effect of it cinnarizine was reduced by subsequent it administration of calcium chloride (0.1 micron mol). 3. The it morphine-induced antinociception was potentiated by the previous it adminsitration of cinnarizine (1.0 micring/rat). The stimated AD50 if morphine was reduced from 10.4 (6.8 to 16.1) to 4.9 microng (3.6 to 6.5) by this dose of cinnarizine. The calculated potency ratio for these values was 2.14 (1.28 to 3.57). A similar potentiation was obtained with it nifedipine, but only when drug was injected in combination with morphine. 4. It is concluded that the antinociception evoked by a systemically injected calcium channel blocker is dependent on passage of the drug across the blood brain barrier to act, at least in part, at a spinal site of action. 5. The mechanism of the antinociception induced by it injected calcium channel blockers appears to depend on the interaction of the drugs with Ca2+ binding sites in the spinal cord and, probably, on the type of voltage-sensitive calcium channel involved

An attempt to reduce the loss of pain and touch sensations in leprosy patients.

An attempt was made to improve the perception of pain and touch sensations at the leprosy lesions. The loss of pain and touch sensations in a lesion was graded using Pain/Touch-Sensation-Testing-and-Grading devices. Application of a solution containing 1 mg of histamine per ml of DMSO, at the affected area decreased the grades of the loss of pain sensation in 11 (31.4%) patients and of touch sensation in 8 (22.8%) patients, out of the 35 patients tested, indicating an improvement in the perception at the lesion. This effect, however, did not persist even for 5 minutes. A higher concentration (2 mg/ml) of histamine produced reduction in the sensory loss in a larger percentage (47% for pain and 35.3% for touch) of patients, though the duration of this effect was still not prolonged.

Influence of testosterone on morphine analgesia in albino rats.

Pain threshold for thermal stimulus after morphine, naloxone alone and naloxone in combination with morphine was studied in male rats before and after three days treatment with testosterone. It was also determined 15 days after gonadectomy and administration of testosterone in such rats. There was significant reduction in morphine analgesia after administration of testosterone and also after gonadectomy. Naloxone increased the pain threshold in gonadectomised rats and it enhanced morphine induced analgesia instead of antagonising it. Naloxone, however, had no effect on morphine analgesia in testosterone treated control rats and gonadectomised rats.

Neuropharmacological actions of some newly synthesized Mannich bases.

Benzamido (alkyl) methyl pyrrolidine Mannich bases were synthetized and subjected to certain neuropharmacological studies. All the bases reduced the pentobarbitone sleeping time and rota-rod grip of rats. The Mannich bases II, III and V raised the minimal electro-shock seizure threshold of rats. The TAB-induced pyrexia was not reduced by the bases I and III in rabbits. None of the bases showed any significant analgesic activity.