Showing papers by "Arthur K. Cho published in 1989"

The effect of optical isomers of 3,4-methylenedioxymethamphetamine (MDMA) on stereotyped behavior in rats

Abstract: The relative potencies of S(+)-, R(−)-3,4-methylenedioxymethamphetamine (MDMA) and S(+)-methylenedioxyamphetamine (MDA) in inducing stereotyped behavior were determined in comparison with p-chloroamphetamine. S(+)-MDMA was more potent than R(−)-MDMA in eliciting stereotyped behaviors such as sniffing, head-weaving, backpedalling and turning and wet-dog-shakes. These results are consistent with the actions of the drug on release of neurotransmitters in which the S(+) enantiomer is more potent. The desmethyl derivative of (+)MDMA, (+)MDA, was more potent than (+)MDMA in eliciting stereotyped behaviors, and produced wet-dog shake behavior.

Characterization of the effects of the acute and chronic administration of phencyclidine on the release of adrenocorticotropin, corticosterone and prolactin in the rat: evidence for the differential development of tolerance.

Abstract: Phencyclidine (PCP) is a widely used drug of abuse; however, little is known of its effects on neuroendocrine function. The present study characterized the effects of the acute and chronic administration of PCP on the release of adrenocorticotropin, corticosterone and prolactin in the rat. For the acute studies, PCP hydrochloride (0.5-10.0 mg/kg s.c.) was administered and the subjects were sacrificed 15 to 300 min later. The acute administration of PCP produced rapid and long-lasting increases in plasma levels of adrenocorticotropin and corticosterone but decreased plasma levels of prolactin. For the chronic studies, PCP (1.0-20.0 mg/kg/day s.c.) was injected daily and the subjects sacrificed 60 min after injection on day 15. PCP continued to stimulate the pituitary-adrenal axis after chronic administration; however, there was a decrease in the magnitude of response, indicating the development of some degree of tolerance. In contrast, none of the doses of PCP tested decreased plasma prolactin levels in chronically treated subjects. There were no differences in plasma or brain levels of PCP in the chronically PCP-treated rats, indicating that tolerance was not due to changes in the biodisposition of PCP. These results indicate that PCP disrupts neuroendocrine function markedly in the rat. The differential development of tolerance to the effects of PCP on the pituitary-adrenal axis and prolactin release may indicate that different neurochemical substrates underlie the effects of PCP on different endocrine systems.

Pharmacokinetic and pharmacodynamic evaluation of phencyclidine and its decadeutero variant.

Abstract: The role of metabolism in the in vivo actions of phencyclidine (PCP) was examined by comparing deuterium-substituted drug with drug of normal isotopic abundance. PCP elicits two responses that differ in their time course, ataxia, which is observable immediately after dosage, and hypothermia, which peaks approximately 90 to 120 min after drug administration. The role of metabolism in these responses was determined by comparing bioavailabilities of deuterium enriched (d10) and normal (d0) PCP with the two responses. Plasma concentration was determined after the i.v. and i.p. administration of d10 and d0 drug and the bioavailability of the d10 was found to be 1.3 to 1.5 times the d0. The clearance of the d10 was also smaller than the d0. The d10, which is pharmacologically equivalent in vitro, is metabolized more slowly than the d0 in vitro. The pharmacokinetic and pharmacodynamic bioavailabilities exhibited comparable isotope effects, indicating that both responses are due to the actions of the parent drug.

Xylamine enhances pineal gland N-acetyltransferase activity in vitro.

Abstract: 1. 1. The action of N-2′-chloroethyl-N-ethyl-2-methyl benzylamine (xylamine) on rat pineal gland sympathetic innervation was examined. 2. 2. This alkylating agent caused a concentration-dependent increase in pineal gland N-acetyltransferase (NAT) activity in neurologically intact pineal glands that was suppressed in glands previously subjected to bilateral superior cervical ganglionectomy. 3. 3. Xylamine-induced elevations in NAT activity were attenuated by β-noradrenergic antagonist drugs but not by α-noradrenergic antagonist drugs. 4. 4. Since pineal gland uptake of radiolabelled norepinephrine (NE) was impaired by xylamine, the drug may increase pineal gland NAT activity by inhibiting NE reuptake into the presynaptic nerve terminal, thereby increasing the amount of the neurotransmitter available to stimulate pinealocyte β-noradrenoceptors.