Beta-blocking relaxant effects on 5-HT induced vascular smooth contractions

This paper describes the effects of the B-adrenergic antagonists betaxolol and timolol on contractions induced by 5-HT in the rat aortic strip. Aortic strips were incubated in an aerated tissue bath containing Kreb's solution and maintained at 37 degree C. A dose response relationship was elicited with 5-HT. We used 0.5 * 10 M 5-HT as a working dose which gave an equivalent contractile response as 30 * 10 M KCL. The relaxant effects of betaxolol and timolol on the tissue precontracted with 5-HT were studied in equimolar doses ranging from 100 * 10 M to 400 * 10 M. Responses with 5-HT were fitted on a dose-response curve with an ED of 1.66 * 10 M. In the presence of equimolar concentrations of timolol and betaxolol (150 * 10 M) the 5-HT response curve shifted to the right displaying competitive antagonism with both betaxolol and timolol. In the presence of betaxolol the Ed of 5-HT was three-fold higher than with timolol, indicating its higher potency and sensitivity at 5-HT receptors. Timolol and betaxolol both significantly anatagonize serotonin induced vasconstriction. THe increase in relaxation demonstrated by betaxolol may be effect through 5-HTIA receptor subtype; this auto regulatory receptor inhibits the vasoconstrictive effect of serotonin. the differential potencies of betaxolol and timolol in antagonizing the vasoconstrictive effects of serotonin suggests the vascular relaxation may be exerted through receptors other than the adrenergics.(AU)

The enhanced effect of the combination of cannasol with timolol and with pilocarpine on intraocular pressure - abstract

Cannasol ophthalmic drop is prepared from the non-psychoactive fraction of Cannabis sativa. The preparation contains 0.1 percent benzalconium chloride as a preservative. Letters Patent have been granted in Jamaica at this time for the eye drop. Timolol and pilocarpine are established eye drops used to treat glaucoma. When Cannasol and timolol are added together, irrespective of the order of combination, there is a precipitous and prolonged fall in the intraocular pressure, both in the dog and in the human. When Cannasol is combined with pilocarpine, the result is the same. Both timolol and pilocarpine produce spikes (rebound) in therapy which can be dangerous to the optic disc. These spikes are not seen when Cannasol is used on its own or used in combination as mentioned above. The enhanced effect with timolol is greater than with pilocarpine and this is to be expected. Timolol is a beeta-adrenoceptor antagonist, while Cannasol is an alpha-adrenoceptor antagonist, while Cannasol is an alpha-adrenoceptor stimulant, both acting to reduce tumour formation. Pilocarpine on the other hand constricts the pupil and widens the filtration angle, a mechanism quited different from that of Cannasol or timolol. This combined effect is now being used to advantage in patients with glaucoma resistant to conventional treatment and who might otherwise need surgery (AU)