Studies on isoxsuprine hydrochloride for the treatment of navicular disease

Abstract

Summary A peripheral vasodilating agent, isoxsuprine hydrochloride, administered as an oral paste, was evaluated to determine its efficacy for the treatment of navicular disease. In a clinical trial, 13 horses with navicular disease were treated at a dose rate of 0.6 mg/kg body weight (bwt) twice daily for periods of six to 14 weeks. Twelve of the horses became completely sound while being treated, although two required a 50 per cent increase in dose. Nine of the horses have remained sound two to 10 months after ceasing therapy. In a controlled randomised double blind clinical trial, 16 horses with navicular disease were assigned to treatment with either a placebo paste or isoxsuprine paste for three weeks and then re‐examined. All the horses treated with isoxsuprine showed improvement in gait, with seven of eight horses becoming sound, whereas only two horses treated with a placebo paste showed slight improvement. This difference in response was highly significant (P<0.001). To evalulate any physiological and biochemical effects of isoxsuprine, it was administered to five Standardbred geldings at dose rates of 0.6 mg/kg bwt and 1.2 mg/kg bwt. Complete blood counts, routine plasma biochemical parameters, cardinal signs and blood pressure measurements were performed up to 24 h after a single dose. No significant change in any of these parameters was found. To assess the peripheral vasodilatory action of isoxsuprine, infra‐red thermography of the lower limb was performed before and up to 8 h after administration to horses. This revealed a significant increase in distal limb temperature which occurred from 90 to 480 mins after isoxsuprine administration. The maximum mean increase in distal limb temperature was 3.1°C and this occurred 4 h after administration of the drug. Résumé On s'est efforcé d'evaluer l'efficacité dans le traitement de la maladie naviculaire d'un vasodilateur périphérique, le chlorhydrate d'isoxsuprine administré en pâte orale. Treize chevaux atteints de maladie naviculaire ont été traités lors d'une épreuve clinique à la dose de 0.6 mg/kg de poids vif, deux fois par jour durant 6 à 14 semaines. Douze de ces chevaux montrèrent une complète guérson fonctionnelle durant le traitement avec pour deux d'entre eux la nécessité d'augmenter la posologie de 50 pour cent. Neuf de ces animaux sont restés utilisables durant une période variant de 2 à 10 mois après la cessation du traitement. Lors d'une épreuve de contrôle, 16 chevaux atteints de maladie naviculaire recurent un traitement sous forme d'un placebo ou d'isoxsuprine en pâte durant 3 semaines et furent ensuite réexaminés. Tous les chevaux traités à l'isoxsuprine montrèrent une amélioration de leurs allures, 7 d'entre eux étant normaux; tandis que deux chevaux traités par placebo montrèrent une amélioration légère. La différence entre les résponses était très significative (P<0.001). Pour évaluer les effets physiologiques et biochimique de l'isoxsuprine, on l'administra à 5 chevaux hongres aux posologies de 0.6 mg et 1.2 mg/kg. Les hémogrammes comp...

An Analgesic Evaluation of Isoxsuprine in Horses

“…Recently, it has been suggested that part of the therapeutic effects of isoxsuprine in horses could be mediated by producing analgesia (Brumbaugh et al., 1999), but our results do not support this hypothesis. This is the first report to assess the analgesic potential of isoxsuprine in horses and gives scientific support to the asseveration that isoxsuprine does not have any analgesic effect in horses (Erkert and MacAllister, 2002), and to the anecdotal report of lack of analgesia of isoxsuprine in horses (Rose et al., 1983).…”

“…In vitro , isoxsuprine produces vasodilatation in blood vessel rings from healthy horses (Baxter et al., 1989; Belloli et al., 2000), an effect attributed to blockade of α 1 ‐adrenoceptors (Belloli et al., 2000). In vivo , increased thermographic temperature of the cannon bone, fetlock and coronary band of forelimbs of horses has been reported after oral isoxsuprine administration, which suggests that isoxsuprine increases blood flow in the distal forelimbs of horses (Rose et al., 1983; Deumer et al., 1991). However, oral and intravenous administration of isoxsuprine did not modify digital or laminar blood flow in healthy horses (Adair et al., 1997; Ingle‐Fehr and Baxter, 1999).…”

“…In domestic animals, it has been used to produce uterus relaxation and to perform obstetric procedures (Fiocre and Rioux, 1974). In horses, isoxsuprine is used as part of the treatment of navicular disease (Rose et al., 1983; Wilson and Bolhuis, 1986; Turner and Tucker, 1989) and laminitis (Kirker‐Head et al., 1986; Sumano et al., 1997; Brumbaugh et al., 1999). In vitro , isoxsuprine produces vasodilatation in blood vessel rings from healthy horses (Baxter et al., 1989; Belloli et al., 2000), an effect attributed to blockade of α 1 ‐adrenoceptors (Belloli et al., 2000).…”

The Effect of Oral Isoxsuprine and Pentoxifylline on Digital and Laminar Blood Flow in Healthy Horses

“…Vasodilation, vasoconstriction, arteriovenous shunts, and coagulation dysfunction have been incriminated as potential mechanisms for the disease 1–3 . Several drugs used routinely in equine practice for the treatment of vascular diseases of the foot, specifically laminitis, are believed to increase digital perfusion by changing vasomotor tone or cardiovascular function 1,4,5 . Isoxsuprine and pentoxifylline are thought to improve digital blood flow in horses 4,6 (JH Boucher, personal communication, 1993), and are used to treat ischemic conditions of the foot such as laminitis and navicular syndrome 4–7 …”

“…Isoxsuprine also inhibits platelet aggregation 12 . In horses with navicular syndrome, improvement in lameness scores has been reported after oral and intravenous (IV) isoxsuprine treatment 4,6,7 . An increase in horse forelimb skin temperature measured by thermography was reported after isoxsuprine administration 4,10 .…”