Effects of psychotropic drugs on canine cerebral metabolism and circulation related to EEG--diazepam, clomipramine, and chlorpromazine.

Abstract

SYNOPSISThe effects of diazepam, clomipramine, and chlorpromazine upon cerebral metabolism and blood flow were examined separately in 18 dogs. After the administration of diazepam or clomipramine, cerebral cortical oxygen consumption (CMRO2) decreased significantly by a maximum of 17% and 13% of control within 10 minutes and 15 minutes, and returned to control at 120 minutes and 90 minutes, respectively. Chlorpromazine, however, decreased by a maximum of 10% of control, a level which continued throughout the period of observation. It was observed that reduction in CMRglucose was followed by the reduction in CMRO2 at an interval during the early stages of CMRO2 depression. Diazepam produced a significant decrease in CBF accompanied by a reduction in CMRO2, but neither clomipramine nor chlorpromazine had any effect on CBF in spite of reduction in CMRO2. Reduction in CMRO2 both with diazepam and clomipramine was accompanied by slow wave activities of EEG, but with chlorpromazine reduction in CMR02 was accompanied with less pronounced slow wave activities. It was concluded that the three drugs examined were cerebral metabolic depressants.It has been generally assumed that the effects of psychotropic drugs upon the central nervous system are related to their therapeutic action in patients with psychiatric disorder. This assumption follows from extensive pharmacological, biochemical, and electrophysiological studies obtained with these drugs. In the present study we examined the effect of three psychotropic drugs-diazepam, clomipramine, and chlorpromazine-on the canine cerebral metabolism and circulation.Although the effects of chlorpromazine on cerebral oxygen consumption have been extensively investigated in animals (Frowein et al., 1955) or men (Fazekas et al., 1955;Morris et al., 1955;Aizawa et al., 1956;Moyer et al., 1956;Ehrmantraut et al., 1957;Sutherland et

Effects of a Diazepam-Fentanyl Mixture on Cerebral Blood Flow and Oxygen Consumption in Man

“…affected the grey compartment onlythe slow component of the flow did not vary. In the group of normal patients, the changes in cbf 10 and CMRo 2 were similar (-34% and -34.5%) and thus resemble the effects of the barbiturates (Pierce, Lambertsen and Deutch, 1964) and Althesin (Sari et al, 1976). The relationship between cbf 10 and Pv Ol is linear and of the same order as that obtained under Althesin (Sari et al, 1976).…”

“…In dogs diazepam alone has been shown to decrease c.b.f. and cause a parallel decrease in CMRo 2 (Maekawa, Sakabe and Takeshita, 1974), the decrease in the flow appearing as early as the second minute after administration (Sari et al, 1975). In comatose patients with diffuse cerebral lesions, the decreases in flow following the administration of diazepam were associated with similar decreases in metabolism (Cotev and Shalit, 1975).…”

Brain temperature effects of intravenous heroin: State dependency, environmental modulation, and the effects of dose

“…While weaker in amplitude and relatively transient in duration (~30 min), these effects are consistent with the CNS depressive action of heroin—a presumed cause of acute, overdose-induced health complications. This decreased metabolic activity coupled with the enhanced heat loss from skin surfaces makes the rat exceptionally susceptible to more dramatic decreases in brain and body temperatures if large-dose heroin use is combined with other drugs with CNS inhibiting and vasodilatory actions such as alcohol (Gillespie, 1967; Volkow et al, 1990) and benzodiazepines (Sari et al, 1975; Abel et al, 1970; Kiyatkin and Bae, 2008). …”

Measurements of Cerebral Oxygen Consumption: Advantages and Limitations

“…can be obtained on a minute-to-minute basis [e.g. Altenlntrg ct al.. 1969;Sari et al, 1975;Meldrum and Nilsson. 1976; in press).…”