P.G. Adaikan

The effect of loperamide on prostaglandin induced diarrhoea in rat and man.

Loperamide, a new antidiarrhoeal compound, effectively antagonised prostaglandin induced diarrhoea in adult healthy male volunteers and in patients undergoing pregnancy termination with prostaglandins. This compound is effective in inhibiting prostaglandin induced fluid accumulation in the small intestine in rats. Loperamide also blocked smooth muscle stimulating action of prostaglandins, acetylcholine and histamine on gastrointestinal smooth muscle preparations from several laboratory animals.

Platelet and other effects of carboprostacyclin - A stable prostacyclin analogue

Carboprostacyclin, a chemically stable analogue of prostacyclin (PGI2) is 12.5 and 25.0 times respectively weaker than PGI2 in inhibiting ADP-induced aggregation of baboon and human platelets in vitro. Carboprostacyclin was also 28.5 times weaker as a vasodepressor than PGI2 in anaesthetised baboons. Intravenous and oral administration of carboprostacyclin in baboons resulted in ex-vivo inhibition of ADP-induced platelet aggregation at doses that did not produce changes in blood pressure or heart rate. Like PGI2, carboprostacyclin contracted guinea pig tracheal chain preparation in vitro but decreased histamine induced lung resistance in anaesthetised guinea pigs. Both PGI2 and carboprostacyclin relaxed the human respiratory tract smooth muscle in vitro.

Inhibition of platelet aggregation with intravenous and oral administration of a carboprostacyclin analogue, 15-cyclopentyl-ω-pentanor-5(E)-carbacyclin (ONO 41483) in man

Intravenous and oral administration of a chemically stable carboprostacyclin analogue, 15-cyclopentyl-omega-pentanor-5(E)-carbacyclin (ONO 41483), resulted in ex-vivo inhibition of ADP-induced platelet aggregation in man. The maximum tolerated intravenous dose was 2.5 ng/kg/min for 1 hour and this produced a mean of 27.1% inhibition in 3 volunteers. For oral administration the tolerated single dose was 200 microgram. At this dose, there was 56.3% inhibition of aggregation (mean of 3 results). High oral (400 microgram) and intravenous doses (5 and 10 ng/kg/min for 1 hour) of ONO 41483, which caused marked inhibition of aggregation (ranging 39-100%), was accompanied by flushing of face and extremities, headache and phlebitis. However, none of the doses tested produced significant changes in arterial blood pressure or heart rate.

Inhibition of platelet aggregation with intravenous and oral administration of carboprostacyclin in man

Intravenous infusion of carboprostacyclin, a chemically stable analogue of prostacyclin (PGI2) resulted in ex-vivo inhibition of ADP-induced platelet aggregation at doses that did not produce significant changes in blood pressure or heart rate. Oral administration of relatively large doses of this compound also inhibited ex-vivo ADP-induced platelet aggregation but this was accompanied by headache, facial flush, tachycardia and changes in blood pressure.

Effect of topical prostaglandins on nasal patency in man

The effect of prostaglandin E1 and 17 phenyl trinor PGE2 on nasal patency has been studied in healthy volunteers and in patients with vasomotor and allergic rhinitis. Both drugs applied topically increased nasal patency. The effect of a single dose of either compound lasted for several hours. Prostaglandin E1 produced nasal irritation and throbbing, lacrimation, headache and sore throat. Except for occasional brief nasal irritation, these side effects were not encountered with 17 phenyl trinor PGE2.

Some pharmacological effects of 17(S) methyl-ω-honiytrans-Δ2-PGE1 (ONO 1206)

Abstract 17(s) methyl-ω-hamo-trans-Δ 2 -PGE, (ONO 1206) produced qualitatively similar effects to PGE 1 in several systems.It was 18.4 and 25.6 times respectively more potent than PGE 1 in inhibiting ADP-induced baboon and human platelet aggregation in vitro. Intravenous infusion of ONO 1206 in baboon also produced ex-vivo inhibition of ADP-induced platelet aggregation.However, this was accompanied by a significant fall in blood pressure and an increase in heart rate. The potent relaxant effect of ONO 1206 on human respiratory tract smooth muscle in vitro suggests that this compound may be a bronchodilator in man.

Effects of some prostaglandin E1 analogues on guinea pig and human respiratory tract.

The effects of (a) 4, 5, 6-trinor-3, 7-inter-m-phenylene PGE1 methyl ester, (b) 4, 5, 6 trinor-3, 7-inter-m-phenylene 3 oxa PGE1 and (c) 4, 5, 6 trinor-3, 7-inter-m-phenylene 3 oxa PGE1 methyl ester on human and guinea pig respiratory tract muscle in vitro and in vivo have been studied. All the analogues relaxed the isolated preparations of guinea-pig tracheal chain, human tracheal, bronchial and bronchiolar muscles and decreased histamine-induced lung resistance in the anaesthetised guinea pig. On some preparations the effects of the analogues were more pronounced than those of PGE1. The results suggest that some of the inter-m-phenylene analogues of PGE1 may be bronchodilators in asthmatics.

Effect of 17 phenyl PGF2α on nasal patency in man

Abstract The effect of three different doses (12.5 μg, 25 μg and 50 μg) of 17 phenyl PGF2α on nasal patency in fourteen patients with vasomotor rhinitis was studied on separate occasions. In all subjects the three doses of the prostaglandin analogue increased nasal patency for varying duration. With the 50 Rg single dose the duration of action ranged between three hours and more than seven hours. There were no side effects in most of the patients.

Non-specific prostaglandin antagonism by 8-ethoxycarbonyl-5-methyl-10, 11-dihydro-PGA1-ethyl ester (HR 546) on some smooth muscle preparations in vitro.

The ability of 8-ethoxycarbonyl-10, 11 dihydro-A-prostaglandin(HR 546) to antagonise smooth muscle contracting effect of prostaglandins E2 and F2alpha on isolated preparations of rat and hamster stomach fundus, guinea pig ileum and gerbil colon has been studied. HR 546 was found to be a potent, non-specific, probably competitive, prostaglandin antagonist on these four smooth muscle preparations.