Water soluble marihuana-derived material: Pharmacological actions in rabbit and primate

Abstract

Further studies have been made with water soluble marihuana-derived material (MDM). Neither adrenergic, cholinergic, aldosterone, dopamine or serotonin antagonism affected the fall in intraocular pressure induced by MDM. Partial blockade was obtained with galactose, glucose, or mannose, but not arabinose, when the latter were given at intravenous concentrations of 1 gm/animal and MDM was given at 25 micrograms animal, suggesting that these sugars may be involved at the active site of the MDM glycoproteins. Dexamethasone was without effect on either intravenous or intravitreal MDM indicating that the MDM effect is not a non-specific response to a protein. A similar plant glycoprotein, larch arabinogalactan, at 200 micrograms/animal was without effect on intraocular pressure. Aqueous humor flow rate was increased 3 hours after MDM administration, a period corresponding to the intraocular pressure increase caused by MDM, and fell to 20% of control values when the fall in intraocular pressure occurred. Blood flow through the iris was increased at both one and six hours after intravenous MDM injection indicating a vasodilation which could contribute to the initial increase in intraocular pressure. Intravitreal injection of MDM in rabbit and rhesus monkey caused a fall in intraocular pressure only after a 24 hour delay: the unilateral response indicated that systemic metabolism was not required for activity and the delay was likely caused by the diffusion time to the ciliary processes from the mid-vitreal injection site. The changes in beta-receptors, adenylate cyclase and carbonic anhydrase in the ciliary processes are minimal indicating a possible vascular mechanism of action of MDM.

Cellular Mechanisms in the Actions of Antiglaucoma Drugs

“…The earlier work was done primarily with the lipid soluble cannabinoids, with differences in activity reported for their abilities to decrease the IOP (208,209). Recent observations with the waterextracted material from marihuana has revealed a more marked effect on IOP than reported for the lipid-soluble extracts (210). The decrease in IOP observed with the water-soluble extract was found to correlate with a reduction in aqueous inflow (211).…”

A Synopsis of Recent Developments in Antiglaucoma Drugs

“…Purer fractions of MDM decreasedlOP In rabbits as much as 50% with no effect on systemic blood pressure or blood chemistry (153). The effect of MDM was thought to be mediated by local vascular action (154). MDM given topically to rabbits and monkeys in doses up to 10% had no effect (155).…”

Centripetal movement of fluorescein dextrans in the cornea: relevance to arcus

“…After transfer to the vials, the corneal portions were allowed to swell for at least 18 to 25 h at room temperature before analysis of fluorescein content of the bathing solution. Fluorophotometric readings were obtained directly from each of the solutions in which the sections of corneas were incubated without dilution, using a Haag-Streit 360 slit-lamp with a Gamma Scientific fluorophotometer attached (Waltman & Kaufman 1970; Green et al 1981Green et al , 1982. Fluorescein concentrations were linear between giml(l72 V output).…”