Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Barbiturates”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 217 records · Page 12Linked to original sources
PubMed1980

On-column gas chromatographic synthesis of 1,3-dialkyl (c = 1-10), benzyl, and cyclohexyl barbiturate derivatives.

Procedures are described for the on-column gas chromatographic synthesis of various N-alkyl-N-alkyl barbiturates where groups added to the nitrogens are benzyl, cyclohexyl, or straight chains with 1 to 10 carbons. The 1,3-dialkyl barbiturates having methyl, ethyl, n-propyl, n-butyl, cyclohexyl, isopropyl, or t-butyl groups can be prepared on-column by injecting an aliquot of a chloroform solution of the barbiturate with the appropriate N,N-dimethylformamide dialkyl acetal. The 1,3-dialkyl barbiturates where benzyl or butyl through decyl groups are added can be similarly prepared with N,N-dimethylformamide dineopentyl acetal and the appropriate alcohol to yield the desired compound. The 1-alkyl (I)-3-alkyl-(II) barbiturates where the alkyl groups differ are prepared by on-column reaction reaction of a barbiturate with aliquots of each of the respective reagents giving the desired groups.

Alkylation↗
PubMed1981

Barbiturate-induced coma therapy for focal cerebral ischemia. Effect after temporary and permanent MCA occlusion.

The authors have studied the therapeutic effect of barbiturate coma following middle cerebral artery (MCA) occlusion in primates. The relationship of the efficacy of barbiturate protection to the presence or absence of recirculation was examined. Barbiturate therapy was begun 30 minutes after MCA occlusion. The findings were as follows: 1) barbiturate-induced coma, with its attendant monitoring, was safely tolerated by primates for 96 hours; 2) 6 hours of MCA occlusion followed by recirculation resulted in a neurological deficit that was worse than the neurological deficit produced by permanent MCA occlusion; 3) barbiturate-induced coma for 96 hours, initiated 30 minutes after the onset of MCA occlusion, in the absence of reperfusion, was in fact detrimental; 4) barbiturate-induced coma for 96 hours, initiated 30 minutes after MCA occlusion, with the establishment of reperfusion at 6 hours, provided nearly complete protection from ischemic damage.

Animals↗
PubMed1975

Simultaneous detection of morphine and barbiturates in urine by radioimmunoassay.

This report describes a radioimmunoassay for the simultaneous detection of morphine and barbiturates. Morphine and barbiturate antibodies, obtained from goats, were mixed with 125l-labeled antigens. By adjusting concentrations of the morphine and barbiturate antibodies and radiolabeled antigens, closely superimposed standard curves for the two drugs would be obtained. As a consequence, similar response curves were obtained for urine specimens containing morphine or barbiturates. Although concentrations as low as 25 mug/liter could be measured, to ensure against false positive reactions the test should be performed at the 100 mug/liter concentration. Unknown samples positive by the dual assay were confirmed by separately testing the specimens with the individual radioimmunoassay specific for morphine or barbiturate. Equivalency tests of urines positive for morphine, positive for barbiturates, or negative for both demonstrated complete correlation between the single and dual assays. The mixed reagent retained its sensitivity and specificity for at least three months when stored at 4 or 25 degrees C. The dual radioimmunoassay is a rapid, simple procedure that can be adapted to automated processes and that is suitable for large- and small-scale screening.

Barbiturates↗
PubMed1991

A barbiturate-regulated protein binding to a common sequence in the cytochrome P450 genes of rodents and bacteria.

Analyses of the 5' regulatory sequences of genes encoding barbiturate-inducible cytochromes P450BM-1 and P450BM-3 from Bacillus megaterium and of the 5' sequences of genes for barbiturate-inducible P450b and P450e of the rat revealed a string of 17 base pairs in each of the genes that shared a high degree of sequence identity. Labeled oligonucleotide probes of each of these four sequences were tested in gel retardation assays with protein obtained from B. megaterium grown either in the presence or absence of barbiturates or with protein from nuclear extracts from livers of rats left untreated or injected with phenobarbital. Each of the four 17-mers bound strongly to a single protein from bacteria grown in the absence of barbiturates, but this binding was dramatically reduced with protein from pentobarbital- or phenobarbital-grown cells. Conversely, the probes complexed weakly to one protein band from nuclear extracts from untreated rats but much more strongly with protein from phenobarbital-treated rats. Similar effects could be obtained by prolonged incubation with phenobarbital of either soluble protein from the bacteria grown in the absence of barbiturates or nuclear extract protein from untreated rats. Deletion analysis of the 5'-flanking region of the P450BM-1 gene of B. megaterium revealed a putative repressor binding site located within a 24-base pair DNA segment that included the 17-base pair sequence involved in barbiturate-regulated protein binding.

Animals↗
PubMed1990

Exposure to barbiturates in utero and during childhood risk of intracranial and spinal cord tumors.

Barbiturate exposure during childhood was assessed from medical records of 237 children with intracranial and spinal cord tumors and 474 matched controls in a prepaid health plan. In utero exposure was also examined in a subset of 86 "cases" and 172 controls whose mothers were health plan members during pregnancy. No association of in utero exposure to barbiturates was found [odds ratio (O.R.) = 0.96, 95% confidence interval (C.I.) = 0.47, 1.94]. An association was noted for barbiturate use during childhood (O.R. = 1.80, 95% C.I. = 1.18, 2.74) but was reduced (O.R. = 1.41, 95% C.I. = 0.89, 2.21) when history of epilepsy was taken into account and was no longer significant. An apparent dose-response effect disappeared after adjustment for a history of epilepsy. Although barbiturate use for epilepsy due to preexisting brain tumors clearly explains some of the observed association, the small, residual risk prevents us from ruling out a possible carcinogenic effect of barbiturates. Further study of cohorts of adult as well as childhood users of barbiturates and other anticonvulsants is recommended.

Adolescent↗
PubMed1987

Barbiturates bind to an allosteric regulatory site on nicotinic acetylcholine receptor-rich membranes.

The ability of barbiturates to bind to acetylcholine receptor-rich membranes purified from the electroplaques of Torpedo nobiliana was examined by centrifugation assay. [14C]Amobarbital both partitioned into the membrane and bound displaceably to a site with an equilibrium dissociation constant of 12 microM. This low affinity made the stoichiometry difficult to obtain despite the high specific activity of acetylcholine receptors in this membrane preparation. However, the data are not inconsistent with a stoichiometry of one barbiturate-binding site per acetylcholine-binding site. Displaceable [14C]amobarbital binding was completely inhibited by barbiturates (IC50: amobarbital, 28 microM; secobarbital, 110 microM; pentobarbital, 400 microM; phenobarbital, 690 microM; butabarbital, 690 microM; and barbital, 5.1 mM. alpha-Bungarotoxin had no effect, but cholinergic ligands that convert the acetylcholine receptor to the desensitized state (acetylcholine, carbamylcholine, and, to a lesser extent, d-tubocurarine) partially inhibited displaceable [14C]amobarbital binding. This cholinergic inhibition was prevented by preincubation with alpha-bungarotoxin, implying an allosteric mediation through the classical cholinergic site. This negative interaction between the cholinergic and the barbiturate sites was mutual with barbiturates partially decreasing equilibrium [3H]acetylcholine binding in a saturable fashion with relative affinities that parallel those for inhibiting [14C]amobarbital binding (IC50). These data establish a mutual negative heterotropic interaction between barbiturate-binding sites and cholinergic binding sites on the nicotinic acetylcholine receptor from Torpedo.

Acetylcholine↗
PubMed1986

Facilitation of recurrent inhibition in rat hippocampus by barbiturate and related nonbarbiturate depressant drugs.

The effects of anticonvulsant, anesthetic and convulsant barbiturates and of related depressant drugs were characterized on excitatory and inhibitory synaptic transmission in slices of rat hippocampus. The duration of recurrent GABAergic inhibition was increased by all of the drugs tested, including the convulsant barbiturate 5-ethyl-5-[1,3-dimethylbutyl]barbituric acid, anesthetic barbiturates such as pentobarbital and nonbarbiturate anesthetics such as (+)-etomidate. Several barbiturates, including phenobarbital and (+)-mephobarbital facilitated inhibition, but the maximal responses to these agents were significantly less than with pentobarbital. In general, there was a good correspondence between the potencies of these drugs in facilitating inhibition and their previously reported abilities to regulate binding at the gamma-aminobutyric acid/benzodiazepine/barbiturate receptor complex. In addition to facilitating recurrent GABAergic inhibition, at successively higher doses most of these drugs induced direct depression of the population spike response, field excitatory postsynaptic potential and presynaptic fiber spike. 5-Ethyl-5-[1,3-dimethylbutyl]barbituric acid, (+)-mephobarbital and pentobarbital facilitated excitatory synaptic transmission at the Schaffer collateral/commissural synapses on the CA1 pyramidal neurons at low doses, but caused depression at higher doses. The net effects observed with each drug tested (facilitation/depression of excitatory transmission, enhancement of GABAergic inhibition) correlated well with the behavioral effects of these agents in vivo.

Animals↗
PubMed1985

Comparative tumor-promoting activities of phenobarbital, amobarbital, barbital sodium, and barbituric acid on livers and other organs of male F344/NCr rats following initiation with N-nitrosodiethylamine.

Tumor-promoting abilities of four barbiturates, phenobarbital [(PB) CAS: 50-06-6], amobarbital [(AB) CAS: 57-43-2], barbital sodium [(BB) CAS: 144-02-5], and barbituric acid [(BA) CAS: 67-52-7], on the development of neoplasms in livers and other organs of rats following initiation with N-nitrosodiethylamine [(DENA) CAS: 55-18-5] were compared. Four-week-old F344/NCr male rats were given a single ip injection of 75 mg DENA/kg body weight. Beginning 2 weeks later, they were given either tap water (group 1) or drinking water containing 500 ppm of PB (group 2), the sodium salt of BB (group 3), AB (group 4), or BA (group 5) for the remaining experimental period. Control groups (groups 6-10) received an ip injection of saline alone and 2 weeks later were given either tap water or drinking water containing barbiturates as listed above. Animals were sacrificed at either 52 weeks or 78 weeks. None of the barbiturates altered the growth and survival of animals. PB and BB increased liver weights and significantly enhanced the development of hepatocellular foci and hepatocellular adenomas at 52 weeks and hepatocellular foci, hepatocellular adenomas, and trabecular carcinomas at 78 weeks in DENA-treated rats. No such enhancing effects were observed with AB or BA. PB or BB did not significantly enhance the incidence of nonhepatic tumors at 52 weeks. However, at 78 weeks BB significantly enhanced the development of renal tubular adenomas and carcinomas, while PB enhanced the development of thyroid follicular cell neoplasms in DENA-treated rats. These results clearly showed that barbiturates exhibited structure-promoting activity relationships and that their promoting abilities were not restricted to liver alone. Substitution of both hydrogen atoms at the C-5 position of the pyrimidine ring by alkyl or aryl groups appears to be essential but not sufficient for tumor-promoting activity of barbiturates.

Amobarbital↗
PubMed1985

Barbiturate-induced alterations in the kinetic parameters of slow outward current in Aplysia giant neurons.

Regulation of spike frequency adaptation has been postulated to be a neuronal mechanism of action of the barbiturates (Zbicz and Wilson, 1981). A barbiturate sensitive slow outward current is present in Aplysia giant neurons, and this current is very effective at regulating adaptation. In the current study a quantitative method of determining the effect of barbiturates was developed using a single-electrode voltage clamp. This method, tail current analysis, involved measuring the exponential decay of the slow outward current at the end of a depolarizing voltage-clamp command. The tail currents were made up of two decay phases with average half-times of 7 and 70 sec, and the tail current amplitude accurately reflected the magnitude of slow outward current. Barbiturates were found to cause a concentration-related, saturable and stereospecific increase in one component of the tail currents, the amplitude of the slow phase. With moderate concentrations of barbiturates there were no changes in the other parameters describing the exponential decay current. The rank order of potency of barbiturates for the enhancement of slow outward current was not well correlated with the lipid solubility of these drugs, indicating that slow outward current enhancement is not due to a nonspecific mechanism, but rather may be receptor mediated.

Action Potentials↗
PubMed1984

Single-reagent polarization fluoroimmunoassay for barbiturates in urine.

We describe a rapid polarization fluoroimmunoassay for screening for the presence of barbiturates in urine. The single reagent is prepared by pre-mixing antiserum with a fluorescein-labeled barbiturate derivative as tracer. Use of a mixture of two sheep antisera, raised against different barbiturate immunogens, results in an assay with a broad cross-reactivity spectrum for most common barbiturates. One adds urine to the pre-mixed reagent, incubates the solution for a few minutes at room temperature, and measures the fluorescence polarization. The tracer/antiserum reagent is stable for at least six months at 4 degrees C. Results compare favorably with two other commonly used screening techniques for barbiturates, thin-layer chromatography and the EMIT-stTM (Syva) system. Although designed as a qualitative screen, some drugs can be quantified by means of a standard curve of the relevant barbiturate.

Barbiturates↗
PubMed1983

Hypothermia and barbiturates: individual and combined effects on canine cerebral oxygen consumption.

Following establishment of total spinal anesthesia, the cerebral metabolic effects of progressive hypothermia (37, 28, 18, and 14 degrees C) were studied initially in six awake dogs. The EEG became isoelectric at temperatures below 18 degrees C. At 14 degrees C, CMRO2 was reduced to 7% of control. Thereafter, 40 mg/kg thiopental, iv, was given and the dogs were rewarmed while an isoelectric EEG was maintained by a continuous thiopental infusion. The CMRO2 was then compared at the different temperatures with and without thiopental. The CMRO2 was unaffected by the barbiturate at 14 and 18 degrees C. At 28 and 37 degrees C the CMRO2 was significantly reduced by the barbiturate (at 37 degrees C to 55% of the 37 degrees C value without thiopental). The change in CMRO2 with temperature in the absence of EEG activity (due to barbiturates) closely approximated an Arrhenius curve (relating log CMRO2 to the reciprocal of absolute temperature). In the presence of EEG activity (no barbiturates) such a simple relationship was less apparent. The results support the following conclusions: barbiturates only affect CMRO2 in the presence of neuronal electrical activity; the combined effect of hypothermia and barbiturates on CMRO2 cannot be expressed as a simple additive relationship; and in the presence of electrical activity, the relationship between temperature and CMRO2 cannot be defined by any simple mathematical function.

Animals↗
PubMed1983

Structure-pharmacokinetic relationships among the barbiturates in the rat.

The pharmacokinetics of a congeneric series of barbituric acids were determined after i.v. administration of individual barbiturates or multicomponent barbiturate mixtures to chronically cannulated male rats. The concentration of barbiturate in plasma and urine was determined using reversed-phase high-performance liquid chromatography. A biexponential equation adequately fitted the plasma-concentration time data. The volume of distribution remained relatively constant within the series. Binding to plasma proteins varied enormously, increasing with lipophilicity. Accordingly, the volume of distribution based on unbound drug also increased with lipophilicity, reflecting a corresponding greater tissue affinity. Total clearance formed a relatively complex nonlinear relationship with lipophilicity. Although the affinity of the barbiturates for erythrocytes increased with lipophilicity, the relationship between total blood clearance and lipophilicity offered no simplification. Renal clearance, the minor route of elimination for the majority of the homologs, decreased with increasing lipophilicity, due to increased tubular reabsorption, whereas nonrenal (hepatic) clearance produced a nonlinear relationship with lipophilicity similar in form to that of total clearance. The nonlinearity of the hepatic clearance within the series was explained by a hepatic blood flow limitation, for the highest homologs, and by the stereochemistry of position 5 on the barbituric acid ring, for the lowest homologs.

Animals↗
PubMed1980

Barbiturates as protective agents in brain ischemia and as free radical scavengers in vitro.

Barbiturates protect the brain in several types of ischemia. The exact mechanism(s) by which they afford protection are unknown. Interest has been focused for the most part on their effects as metabolic depressants, but a slowing energy consumption rate in the ischemic brain cannot explain protection in all ischemic situations. Other propositions for the protective mechanisms of barbiturates include alterations in blood flow distribution, membrane stabilization as well as antioxidant and free radical scavenging properties. We have studied the inhibitory effects of various barbiturates on iron- and ascorbic acid-stimulated lipid peroxidation in brain tissue in vitro. While thiopental was highly efficient, other barbiturates had no (phenobarbital, pentobarbital) or only minor (methohexital) inhibitory effects. The findings were confirmed by studies of the scavenging properties of these barbiturates with a different system (1,1 diphenyl-2-picryl hydrazyl). Since all tested barbiturates protect in brain ischemia in vivo, our results do not support the hypothesis that they protect by acting as free radical scavengers.

Animals↗
PubMed1981

Comparison of ethanol and barbiturate physical dependence.

The physical dependence and tolerance characteristics of barbiturates and ethanol were compared. One group of cats was given anesthetic doses of pentobarbital chronically to produce severe physical dependence ("high dose" group). Two other groups of animals were given barbital or ethanol at "chronically equivalent" doses which produced gross ataxia without anesthesia ("low dose" groups). The doses required to produce the preset level of central nervous system depression progressively increased in all three groups during the chronic administration. Functional tolerance estimated by measuring the drug concentration in the blood at the peak of the drug response was demonstrated in all three groups. Drug administration was terminated after various durations and withdrawal was rated. Severity of withdrawal was assessed by monitoring spontaneous convulsions and by rating motor, autonomic and behavioral signs. These ratings were used to compute peak intensity of withdrawal. The number of convulsions, incidence of lethality during withdrawal and peak withdrawal intensity ratings were considerably higher in the ethanol groups than in the low dose barbiturate groups. Similarly, the number of convulsions, incidence of lethality during withdrawal and peak intensity ratings were consistently higher in the high dose barbiturate groups than in the low dose barbiturate groups. The results indicate that ethanol produced more severe withdrawal than barbiturate when the level of chronic intoxication was comparable in the two groups. Also, the level of central nervous system depression during administration was an important factor influencing intensity of barbiturate withdrawal.

Alcoholism↗
PubMed1980

[Long-term hemodialysis in acute barbiturate intoxication (author's transl)].

From 1975 to 1978, ten patients were on long-term hemodialysis due to acute barbiturate intoxication. Duration of hemodialysis varied from 16 to 40 hours (mean 23 +/- 9.4 hours). Phenobarbital was the most common type of barbiturate ingested (6 out of 10 patients), and diazepam the drug most frequently taken in association with barbiturates (3 out of 10 patients). All patients were in a state of deep unconsciousness (coma II: 1 case; coma III: 5 cases; coma IV: 4 cases), and all of them required endotracheal intubation. Seven patients needed the assistance of automatic intermittent positive-pressure respirator. Two patients presented hypothermia, and another a peripheral collapse. Long-term hemodialysis was well tolerated without major complications. Significant decreases of barbiturate levels were obtained in all cases (before hemodialysis: 7.3 +/- 1.9 mg/dl, after hemodialysis: 1.8 +/- 1.2 md/dl, corresponding to the pattern of secobarbital used to refer the results). No correlation was observed between initial levels of barbiturates and number of hours of long-term hemodialysis required. Neurologic symptoms improved in all cases. Eight patients were conscious after hemodialysis had been discontinued, and only two patients remained unconscious (coma I). Intratracheal tube could be removed in six patients, but positive-pressure respirator could be took away from all cases. Complete recovery was achieved in eight patients. Two patients died on the 2nd. and 8th. postdialysis days due to respiratory distress. Long-term hemodialysis has proven of value in the treatment of severe barbiturate intoxication, particularly better to conventional hemodialysis.

Adolescent↗
PubMed1981

Barbiturate enhancement of GABA-mediated inhibition and activation of chloride ion conductance: correlation with anticonvulsant and anesthetic actions.

The anesthetic-sedative barbiturate pentobarbital (PB) and the anticonvulsant barbiturate phenobarbital (PhB) were applied to mammalian spinal cord neurons in primary dissociated cell culture to assess their effects on: (1) postsynaptic GABA-responses; (2) paroxysmal activity produced by the convulsant bicuculline; (3) resting membrane properties; and (4) spontaneous neuronal activity. The results demonstrated that: (1) anticonvulsant actions occurred at barbiturate concentrations which augmented GABA-responses; (2) anesthetic actions occurred at barbiturate concentrations which produced direct increases in chloride conductance; (3) both anticonvulsant and anesthetic actions occurred at clinically relevant concentrations; and (4) concentrations of PhB, but not PB, which produced GABA-augmentation and direct conductance changes were widely separated. These findings support the hypotheses that augmentation of GABA-mediated inhibition and possibly reduction of glutamate (GLU)-mediated excitation form the basis at least in part for barbiturate anticonvulsant action and that addition of direct increases in chloride conductance to augmentation of GABA-mediated inhibition and reduction of GLU-mediated excitation may partially underlie anesthetic-sedative barbiturate action.

Animals↗
PubMed1993

Acute, chronic and differential effects of several anesthetic barbiturates on glutamate receptor activation in neuronal culture.

The acute and chronic effects of several anesthetic barbiturates, in therapeutic concentrations, on the excitatory amino acid (EAA)-induced elevation of intracellular calcium levels ([Ca2+]i) were examined in neuronal tissue culture. The ultrashort-acting barbiturate, thiamylal, was effective in blocking elevations of [Ca2+]i induced by kainate, N-methyl-D-aspartate (NMDA), and quisqualate or by membrane depolarization with 40 mM KCl. The structurally similar barbiturate, secobarbital which differs from thiamylal only by having an oxygen in place of a sulfur, was able to block elevations induced by the above EAAs but was less effective than thiamylal and did not significantly reduce [Ca2+]i that resulted from membrane depolarization with KCl. Pentobarbital, while differing from secobarbital by only a methyl group, was without effect on either the NMDA- or 40 mM KCl-induced elevations of [Ca2+]i. By contrast, cyproheptadine, a compound that has been shown to block Ca2+ channels, has a different profile from the above barbiturates in that cyproheptadine is more effective in blocking elevation of [Ca2+]i induced by membrane depolarization with KCl while the barbiturates are more effective in reducing [Ca2+]i induced by EAAs. An anticonvulsant barbiturate, phenobarbital, did not reduced elevations of [Ca2+]i induced by any EAA tested or by membrane depolarization with KCl. When cells were treated chronically with thiamylal for 4 days, 2-6 h after the abrupt drug withdrawal there was a hyperresponsiveness to the elevations of [Ca2+]i induced by both kainate and NMDA but not by quisqualate. A similar hyperresponsiveness was not seen after the chronic treatment with phenobarbital.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Barbiturates modulate the activity of the pituitary 3 alpha-hydroxysteroid oxidoreductases and inhibit their production of 3 alpha,5 alpha-tetrahydroprogesterone.

The effects of sodium phenobarbital and sodium barbital on the activity of the particulate and cytosolic 5 alpha-dihydroprogesterone 3 alpha-hydroxysteroid oxidoreductases (3 alpha-HSORs) of female rat anterior pituitary were investigated. By altering the 3 alpha-HSOR catalyzed conversion of 5 alpha-dihydroprogesterone (5 alpha-DHP) to 3 alpha,5 alpha-tetrahydroprogesterone (3 alpha,5 alpha-THP), these barbiturates could influence the in situ production of 3 alpha,5 alpha-THP. 3 alpha,5 alpha-THP has potent barbiturate-like effects on brain GABAA receptors. Both phenobarbital and 3 alpha,5 alpha-THP can affect gonadotropin release in female rats. In vitro incubations of each 3 alpha-HSOR activity were assayed in the presence of sodium phenobarbital (0.1 to 10.0 mM) or sodium barbital (1.0 to 10.0 mM). Since both 3 alpha-HSOR activities catalyze the reversible oxidoreduction of 5 alpha-DHP and 3 alpha,5 alpha-THP, we examined the effect of these barbiturates not only on the conversion of 5 alpha-DHP to 3 alpha,5 alpha-THP (reductive reaction) but also on the "back conversion" of 3 alpha,5 alpha-THP to 5 alpha-DHP (oxidative reaction). The results indicate that both phenobarbital and, to a lesser extent barbital, significantly affected the activities of the two 3 alpha-HSORs in both reductive and oxidative directions. In the reductive direction, phenobarbital inhibited the activity (33%) of both cytosolic and particulate enzymes which would presumably decrease the levels of 3 alpha,5 alpha-THP. In the oxidative direction, a pattern of stimulation was observed (20 to 100%). Thus, this stimulatory effect on the oxidative conversion of 3 alpha,5 alpha-THP to 5 alpha-DHP, which would presumably also decrease 3 alpha,5 alpha-THP levels, appears correlated with the inhibitory effect of these barbiturates on the reductive conversion of 5 alpha-DHP to 3 alpha,5 alpha-THP. Sodium barbital exhibited somewhat similar effects. These changes suggest that barbiturates can lower 3 alpha,5 alpha-THP levels in the anterior pituitary. The results also suggest the possibility that lowered 3 alpha,5 alpha-THP levels may be involved, at least in part, in the reduction of gonadotropin release by barbiturates.

3-Hydroxysteroid Dehydrogenases↗