Pikamilon-a new vasoactive and nootropic preparation

It has therefore been suggested that a combination of nicotinic acid and GABA in the same molecule would potentiate the action of each component. Compound nicotinoyl-~-aminobutyric acid was first synthesized at the All-Union Vitamin Research Institute in 1970 [ii], and in the subsequent years the product pikamilon, created on its basis, has been widely studied both experimentally and clinically. Pikamilon, a sodium salt of N-nicotinoyl-~-a minobutyric acid, is a white crystalline odorless and hygroscopic powder, readily soluble in water. It was shown when the research had only begun that the compound passes rapidly through the BBB. The essential role of GABA in the central and peripheral regulation of the cerebral circulation [4, 14, 15, 17] and also the presence of a nicotinic acid residue possessing vasoactive properties, determined the priority given to the study of the cerebrovascular properties of pikamilon. In experiments on animals pikamilon had a positive action on the cerebral circulation and also exhibited the properties of a tranquilizer with stimulating component [7]. The action of the compound on the cerebral circulation and on its nervous regulation was studied in experiments on anesthetized cats, on conscious, unrestrained cats, and on unanesthetized rabbits. Pikamilon was shown to stimulate the cerebral circulation and to lower vascular tone in both arterial systems of the brain. The increase in the blood supply to the brain in conscious animals took place to a more marked degree than in cats under general anesthesia. The drug also lowered the blood pressure. It must be emphasized that these effects were manifested after both intravenous and peroral administration of the compound. In anesthetized cats, pikamilon in a dose of i0 mg/kg, given by intravenous injection, increased the blood flow by 28  3%, but when given internally -- by 18  1.7%; in conscious animals it was increased by 63  10% and the effect lasted 120-150 min. The increase in the blood flow in unanesthetized rabbits was 42  7.3% by Intravenous injection and 24  8% by the peroral route. In the strength and duration of its cerebrovascular effect, pikamilon is much superior both to GABA and to nicotinic acid. Under the same experimental conditions GABA in a dose of i0 mg/kg (intravenously) caused no change in the cerebral bloodflow, and only when given in a dose of 300 mg/kg did it increase the blood flow into the brain by 20  2.9%, the effect lasting 3-5 min. Nicotinic acid, also in large doses (50-100 mg/kg) increased the cerebral blood flow temporally on average by 5-10%. In its effect on the cerebral circulation, in comparative experiments pikamilon was more effective than papaverine, nialamide, complamin (xantinol nicotinate), and dihydroergotoxin (redergin). An essential role in the mechanism of action Of pikamilon is played by its effect on nervous control of the cerebral circulation. It weakens changes in the cerebral blood flow during the vasomotor reflex, considerably inhibits constrictor responses of vessels of the