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Biomedical subjects

K W Perry

Publications and source records attributed to K W Perry.

At least 109 records · Page 6Linked to original sources
PubMed1975

Reversible and irreversible phases of serotonin depletion by 4-chloroamphetamine.

Pretreatment of rats with an agent that inhibits uptake into serotoninergic neurons [Lilly 110140: 3-(p-trifluoromethylphenoxy)-N-methyl-3-phenylpropylamine hydrochloride] prevented the depletion of brain serotonin by 4-chloroamphetamine, presumably by preventing the entry of 4-chloroamphetamine into the serotonin neuron. When the uptake inhibitor was given after 4-chloroamphetamine, the lowering of both serotonin and tryptophan hydroxylase levels in brain was reversed. Serotonin levels returned to normal after 110140 administration to 4-chloroamphetamine-treated rats at a rate similar to the calculated rate of serotonin turnover in rats treated with 110140 alone. Progressively less reversibility of the 4-chloroamphetamine effect occurred when 110140 was injected at 8, 16 and 24 hr after 4-chloroamphetamine, and no reversibility was observed when 110140 was injected at 32 or 48 hr after 4-chloroamphetamine. These findings indicate that the depletion of brain serotonin by 4-chloroamphetamine is initially reversible but that there is a gradual transition into an irreversible effect between 24 and 48 hr after 4-chloroamphetamine injection. Apparently the prolonged presence of 4-chloroamphetamine inside the serotonin neuron produced by continual reuptake of 4-chloroamphetamine is required for the semi-permanent depletion of brain serotonin stores.

Amphetamines↗
PubMed1975

Effect of 3-(p-trifluoromethylphenoxy). N. N. methyl-3-phenylpropylamine on the depletion of brain serotonin by 4-chloroamphetamine.

3-(p-Trifluoromethylphenoxy)-N-methyl-3-phenylpropylamine (Lilly 110140), when injected into rats at i.p. doses of 1 to 10 mg/kg, prevented the lowering of brain serotonin by 4-chloroamphetamine. The duration of 110140 action was very long, significant antagonism of 4-chloroamphetamine action being apparent still at 48 hours after a single dose of 10 mg/kg of 110140. The N,N-dimethyl tertiary amine derivative was as effective as 110140 itself in antagonizing serotonin depletion by 4-chloroamphetamine, but other structurally related compounds has less activity or were inactive. Likewise, six tricyclic antidepressant drugs injected at 10 mg/kg i.p. did not antagonize the action of 4-chloroamphetamine. When injected into rats whose brain serotonin levels had already been depleted by 3-hour pretreatment with 4-chloroamphetamine, 110140 terminated the action of 4-chloroamphetamine and permitted serotonin levels to return to normal. Lilly 110140 did not antagonize the depletion of brain serotonin or norepinephrine by reserpine, which implies that reserpine does not require the membrane pump for entry into the neuron. The depletion of brain serotonin, but not norepinephrine, by alpha-ethyl-3-hydroxy-4-methylphenethylamine (H75/12) was blocked by 110140. In contrast to chlorimipramine, 110140 did not antagonize the depletion of norepinephrine levels in heart and spleen by 6-hydroxydopamine. The data suggest that 110140 is a specific drug for inhibiting uptake into serotoninergic neurons in the brain.

Amphetamines↗
PubMed1975

Biochemical pharmacology of some chlorinated 3-phenyl-piperidines in rats.

Chlorinated 3-phenyl-piperidines were administered to rats with the expectation--based on structural similarities--that they might resemble chlorinated amphetamines pharmacologically. The 3-chloro, 4-chloro, and 3,4-dichloro compounds all lowered serotonin and 5-hydroxyindoleacetic acid levels in rat brain, whereas the 2-chloro compound had no effect. The brain levels and half-lives of the four compounds suggested that the compounds might be metabolized by hydroxylation at the 4- position of the phenyl ring. Desmethylimipramine, an inhibitor of amphetamine hydroxylation in the 4- position, markedly elevated brain levels of the 2-chloro compound and to a lesser extent of the 3-chloro compound. The 2-chloro compound did not lower brain serotonin levels even in desmethylimipramine-treated rats, however. The results suggest that some pharmacologic properties of the chlorinated 3-phenyl-piperidines are indeed similar to those of chlorinated amphetamines.

Amphetamine↗