4-(p-Chlorophenylthio)butanol (W-2719), a compound that inhibits histamine release from sensitized leukocytes also decreased tracheal smooth muscle tonus, inhibited synthesis and release of immunologically induced SRS-A (slow-reacting substance of anaphylaxis) in the rat and antagonized the in vitro activity of SRS-A. Furthermore, it significantly inhibited the platelet release reaction induced by collagen in vitro but not ex vivo. On the other hand, W-2719 did not possess marked CNS activity nor did it adversely affect the blood pressure, heart rate or respiratory rate. There was no evidence for sympathetic or parasympathetic activity. It had weak antipyretic activity, but exhibited no anti-inflammatory or analgesic activity.

01 Jan 1979·Arzneimittel-Forschung

Acute and subacute (30-day) toxicological investigations of 4-(p-chlorophenylthio) butanol (W-2719) in mice, rats and dogs.

Article

Author: Banerjee, B N ; Ludwig, B J ; Ivins, N J ; Sofia, R D

The acute and subacute toxicity of 4-(p-chlorophenylthio) butanol (W-2719), on anti-allergy agent, was investigated in mice, rats and dogs. Acute LD50 values in the mouse (1145.0 mg/kg p.o.) and rat (greater than 1400.0 mg/kg p.o.) and maximum tolerated dose in the dog (420.0 mg/kg p.o.) were very high, indicative of a high degree of safety following a single oral dose. The subacute toxicity studies were conducted by repeated daily oral administration of the compound for 30 days. In the rat, W-2719 did not produce any significant toxicity up to a dose level of 100.0 mg/kg/day, when administered as a drug-diet admixture. A higher dose, i.e., 200.0 mg/kg/day, produced marked reductions in body weight gain, food consumption, RBC and WBC (females especially), and other hematological parameters. In the purebred beagle dog, W-2719 did not produce any significant toxicity up to a dose level of 100.0 mg/kg/day, the highest dose level tested in this species.

01 Jan 1979·Arzneimittel-Forschung

Metabolism and pharmacokinetics of 4-(p-chlorophenylthio)butanol (W-2719) in the rat and dog.

Article

Author: Schuster, E ; Shahinian, S ; Kucharczyk, N ; Sofia, R D ; Ballard, F H ; Myers, G ; Edelson, J ; Yang, J ; Ludwig, B J

4-(p-Chlorophenylthio)butanol (W-2719) administered orally to rats and dogs is rapidly absorbed, metabolized and excreted. The only major biotransformation product found in blood was p-chlorophenylthioacetic acid (W-2683). No W-2719 or the intermediary p-chlorophenylthiobutyric acid (W-2718) could be found in plasma after oral administration of the drug. When W-2719 was given i.v. to dogs, both W-2719 and W-2718 appeared in plasma but each had a very short half-life of about 10 min. After an oral dose of W-2719 to dogs the plasma content of W-2683 peaked at 4-6 h, amounting to approximately 20% of the dose. More than 91% of the dose was excreted with 48 h, 83% in urine and 9% in feces. The predominant excretion product in urine was p-chlorothiophenol, most of which was excreted in a conjugated form. The other major urinary metabolite was W-2683, while smaller amounts of W-2718 and unchanged drug were also found. No significant effect of prolonged dosing of 14C-W-2719 to dogs was observed on plasma 14C levels, peak time, 14C half-life or excretion and composition patterns.

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Indication	Highest Phase	Country/Location	Organization	Date
Dermatitis, Allergic Contact	Phase 1	-	Meda AB	-

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