Effects of barbiturates, phencyclidine, ketamine and analogs on cerebral circulation and cerebrovascular muscle.
Although barbiturates are often effective as therapeutic agents in several types of brain ischemia, there is no consensus as to their mechanisms of action. Exactly why other intravenous anesthetics such as ketamine are not effective therapies in brain ischemia is not known. Structural analogs of ketamine such as phencyclidine (PCP) not only exert potent hallucinogenic properties and are widely abused drugs, but often result in hypertensive encephalopathies and death. In view of the paucity of information on the cerebral circulatory actions of barbiturates, ketamine and PCP (and analogs), in-vivo (microcirculatory) and in-vitro studies were undertaken. Barbiturates, in anesthetic concentrations (e.g., 10(-5) to 10(-4) M), were found to exert direct vasodilator actions on cerebral arterial smooth muscle; these relaxant actions appear to be related to inhibition of calcium ion (Ca2+) influx in cerebral vessels. The latter may be important in the salutory actions of barbiturates in brain ischemia, head trauma and cerebrovasospasm. Unlike barbiturates, ketamine was found to exert spasmogenic actions on cerebral arteries, which may aid in explaining the inability of this anesthetic to be of therapeutic value in brain ischemia. PCP and its analogs, as well as other hallucinogenic molecules (e.g., LSD, mescaline) produced spasms in cerebral arterioles, venules and arteries in concentrations which mimic their hallucinogenic potencies. Distinct PCP-like receptors which subserve contraction appear to exist on large as well as microscopic cerebral blood vessels. Spasms induced by PCP, its analogs and ketamine can be readily reversed or prevented completely by calcium channel blockers. The latter agents could be quite useful, clinically, in prevention of cerebral infarction, hypertension and fatality associated with PCP (and analogs) intoxication.
D001463:Barbiturates / Q000494:pharmacology*; D001808:Blood Vessels / Q000187:drug effects; D001921:Brain / Q000098:blood supply; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006213:Hallucinogens / Q000494:pharmacology; D006801:Humans; D002546:Ischemic Attack, Transient / Q000139:chemically induced / Q000517:prevention & control; D007649:Ketamine / Q000494:pharmacology*; D008833:Microcirculation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010622:Phencyclidine / Q000031:analogs & derivatives / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D001463:Barbiturates; D002121:Calcium Channel Blockers; D006213:Hallucinogens; D014665:Vasodilator Agents; D007649:Ketamine; D010622:Phencyclidine; D011188:Potassium