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Biomedical subjects

L L Simpson

Publications and source records attributed to L L Simpson.

At least 109 records · Page 6Linked to original sources
PubMed1976

A comparison of the abilities of chlorpromazine and molindone to interact adversely with guanethidine.

Chlorpromazine and molindone were tested for their abilities to impair conditioned avoidance behavior of rats. Chlorpromazine was effective within the dose range of 0.3 to 7.0 mg/kg (ID50approximately 2.0 mg/kg); molindone was effective within the range of 0.3 to 5.0 mg/kg (ID50 approximately 0.6 mg/kg). Behaviorally relevant doses of chlorpromazine and molindone were then tested for their effects on blood pressure and on adrenergic mechanisms. When given intravenously to anesthetized, hypertensive animals, both drugs (1.0 mg/kg) produced significant but transient vasodepression. When given intraperitoneally to anesthetized or to conscious hypertensive rats, the drugs did not produce significant effects on blood pressure. Both drugs (1.0 mg/kg) blocked responses to an alpha agonist (methoxamine), but chlorpromazine was significantly more potent than molindone. In addition, chlorpromazine produced a dose-dependent (1.0-10.0 mg/kg) inhibition of 3H-l-norepinephrine uptake into heart, but molindone at the same doses produced no inhibition of uptake. In related experiments, it was found that guanethidine (50 mg/kg) was an effective agent for lowering blood pressure of hypertensive rats. When chlorpromazine (3-10 mg/kg) was administered concomitantly with guanethidine, the blood pressure lowering properties of guanethidine were diminished or abolished. When molindone (1-10 mg/kg) was administered concomitantly with guanethidine, there was no loss of blood pressure control. It is concluded that molindone is an important drug, because it is an antipsychotic agent that does not interact adversely with guanethidine.

Animals↗
PubMed1976

The role of acetylcholine receptors and acetylcholinesterase activity in the development of denervation supersensitivity.

Strips of muscle from innervated and denervated rat hemidiaphragm were tested for sensitivity to acetylcholine and to carbachol. For both agonists, denervation (6-8 days) produced notable supersensitivity. However, the increase in sensitivity to acetylcholine (ca. 600-fold) was much greater than that to carbachol (ca. 51-fold). Denervation also produced an increase in [3H]alpha-bungarotoxin binding (ca. 20-fold), presumably indicative of an increase in the number of acetylcholine receptors. In addition to causing increases in tissue sensitivity and receptor number, denervation caused a marked loss of acetylcholinesterase activity (ca. 70%) and a modest loss of butyrylcholinesterase activity (ca. 20%). When innervated muscle was pretreated with eserine (5 X 10(-5) M), there was a loss of acetylcholinesterase activity (ca. 86%) and butyrylcholinesterase activity (ca. 36%). Simultaneously, there was an increase in tissue sensitivity to acetylcholine (ca. 26-fold). When denervated muscle was pretreated with eserine, there was no loss of enzyme activity beyond that caused by denervation. Furthermore, eserine pretreatment did not increase denervated muscle sensitivity to acetylcholine. The data suggest that both an increase in acetylcholine receptors and a decrease in acetylcholinesterase activity contribute to the phenomenon of denervation supersensitivity.

Acetylcholine↗
PubMed1975

Blood pressure and heart rate responses evoked by d- and l-amphetamine in the pithed rat preparation.

Isomers of amphetamine were tested for their ability to evoke changes in the spontaneous motor behavior of rats. d-Amphetamine was effective within the dose range of 0.2 to 2.0 mg/kg; l-amphetamine was effective within the range of 1.0 to 10.0 mg/kg. Both d- and l-amphetamine were also compared for their pressor and tachycardic activity in pithed rats. The doses of amphetamine tested (0.1-10.0 mg/kg) were identical to those which produced changes in behavior. d-Amphetamine was approximately 5-fold more potent than l-amphetamine in evoking pressor responses and approximately 3-fold more potent in evoking tachycardic responses. The two isomers differed little in their ability to block norepinephrine uptake into heart. The ID50 values were; d-amphetamine 0.7 mg/kg; l-amphetamine, 1.2 mg/kg. Cocaine, which also blocked norepinephrine uptake into heart (ID50 = 3.0 mg/kg), lacked significant pressor or tachycardic activity in pithed, adrenalectomized animals. The inability of cocaine to evoke responses was related to the marked reduction in norepinephrine turnover and release in pithed animals. It was concluded that differences in potency between d- and l-amphetamine cannot be explained on the basis of blockade of norepinephrine uptake. The difference may relate to evoked release of amine.

Adrenal Glands↗
PubMed1975

An analysis of the sympathomimetic activity of 6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (TIQ).

The pithed rat preparation has been used to study the sympathomimetic activity of 6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (TIQ). In this preparation, an increase in blood pressure is indicative of alpha stimulation, and an increase in heart rate is indicative of beta stimulation. Using this preparation, we have found that TIQ is approximately 3 orders of magnitude less potent than norepinephrine in evoking changes in blood pressure and heart rate. The activity of TIQ has also been studied in pithed animals which had been previously sympathectomized with 6-hydroxydopamine. Sympathectomy produced a marked reduction in cardiac norepinephrine, and it nearly abolished vascular responses to injected tyramine. Following sympathectomy, pithed animals were supersensitive to norepinephrine and subsensitive to TIQ. Similar results were obtained on pithed animals that had been pretreated with cocaine. It is concluded that TIQ is a weak sympathomimetic agent possessing both directly and indirectly acting properties. The data are discussed in terms of a proposal that TIQ may be a false adrenergic transmitter.

Adrenergic alpha-Agonists↗
PubMed1974

The effect of prostaglandin E2 on the arterial blood pressure of normotensive and spontaneously hypertensive rats.

1 In anaesthetized rats, injection of prostaglandin E(2) (0.5-5.0 mug/kg i.v.) caused a dose-dependent vasodepressor response. The magnitude of response was significantly greater in spontaneously hypertensive rats than in normotensive rats.2 In spontaneously hypertensive rats, the magnitude of the prostaglandin-induced depressor response was closely correlated with blood pressure. The higher the blood pressure, the greater was the response evoked by prostaglandin.3 In spontaneously hypertensive rats, a combination of guanethidine plus hydralazine reduced both blood pressure and prostaglandin-induced depressor responses.4 Spontaneously hypertensive rats and normotensive rats did not differ in the magnitude of their vasodepressor responses to intravenously administered acetylcholine or isoprenaline.

Acetylcholine↗