Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Benserazide”

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 145 records · Page 8Linked to original sources
PubMed1994

Effect of type A and B monoamine oxidase selective inhibition by Ro 41-1049 and Ro 19-6327 on dopamine outflow in rat kidney slices.

1. The influence of pargyline and of selective inhibitors of type A and B monoamine oxidase (MAO), Ro 41-1049 and Ro 19-6327 respectively, on the outflow of dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) in slices of rat renal cortex loaded with exogenous L-3,4-dihydroxyphenylalanine (L-DOPA) was examined. Dopamine and DOPAC in the tissues and in the effluent were assayed by means of h.p.l.c. with electrochemical detection. 2. The levels of newly-formed dopamine and DOPAC in the perifusate decreased progressively with time. In control conditions, DOPAC/dopamine ratios in the perifusate were 3 to 5 fold those in the tissue and were found to increase progressively with time. The addition of pargyline (100 microM), produced a marked decrease in the outflow levels of DOPAC (45 to 54% reduction) and significantly increased the levels of dopamine in the effluent (102 to 158% increase); DOPAC/dopamine ratios in the perifusate remained stable throughout the perifusion and were similar to those found in the tissues. The addition of the MAO-A inhibitor Ro 41-1049 to the perifusion fluid also significantly decreased DOPAC outflow (41% to 54% reduction) and increased dopamine outflow (19% to 80% increase). In the presence of Ro 41-1049 DOPAC/dopamine ratios in the perifusate were lower (P < 0.01) than in controls; in contrast with the effect of pargyline, this ratio was found to increase (P < 0.01) throughout the perifusion period. Ro 19-6327 did not reduce the outflow of DOPAC, but significantly increased (by 40-60%) that of dopamine. In the presence of Ro 19-6237, the proportion of DOPAC to dopamine in the perifusate was similar to that of controls and significantly increased throughout the perifusion; however, this increase was less than that observed in the control group.3. When benserazide (50 microM) was added to the perifusion fluid, the levels of both dopamine and DOPAC in the effluent were similar to those observed in the absence of benserazide. However, in the presence of benserazide, DOPAC/dopamine ratios in the perifusate did not increase with time. In conditions of decarboxylase inhibition, the effects of pargyline, Ro 41-1049 and Ro 19-6327 on dopamine and DOPAC outflow were less pronounced than in experiments conducted in the absence of benserazide.4. In conclusion, the results presented here show that the fraction of newly-formed dopamine which leaves the compartment where the synthesis has occurred is a constant source for deamination into DOPAC. The results provide evidence favouring the view that MAO-A is the main form of the enzyme involved in this process; however, the data described here suggest that dopamine would also have access to MAO-B.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1982

Central cardiovascular effects of L-DOPA and clonidine in the lizard, Agama caudospinosa.

The effects of L-DOPA alone and in combination with two inhibitors of 1-aromatic-amino acid decarboxylase (DC), carbidopa and benserazid on the blood pressure (BP) and catecholamine (CA) content in the heart and brain has been investigated in the lizard Agama caudospinosa. The effect of clonidine on BP has also been examined in intact lizards and after spinal cord transection. It is concluded that dopamine (DA) is formed from L-DOPA in brain and heart and that carbidopa reduces the DA formation in the heart but penetrates the blood brain barrier (BBB) poorly, allowing a central decarboxylation of L-DOPA. Benserazid, on the other hand, penetrates the BBB and inhibits the central as well as the peripheral synthesis of DA from L-DOPA. L-DOPA in combination with carbidopa lowers the BP significantly in lizards tilted 45 degrees (head upwards) whereas the supine BP is unaffected. Benserazid pretreatment abolishes the decrease in BP after L-DOPA. L-DOPA alone does not produce any consistent changes in BP. Clonidine lowers BP in intact, tilted animals, while the BP is increased in spinal animals. The results indicate a central mode of action of L-DOPA as well as clonidine in the lizard studied.

Animals↗
PubMed1981

Growth hormone and prolactin stimulation by Madopar in Parkinson's disease.

Madopar, a combination of levodopa with benserazide, induced an inconsistent rise in plasma growth hormone in unmedicated patients with Parkinson's disease and in controls, and a greater growth hormone rise in Parkinsonian subjects on chronic Madopar therapy. In subjects on chronic therapy with levodopa and carbidopa (Sinemet), the growth hormone releasing effect of Madopar was blunted. Madopar increased plasma prolactin (PRL) in controls, unmedicated patients and patients on Madopar therapy while in patients on Sinemet therapy the PRL-releasing effect of Madopar was strikingly reduced. Since these data were interpreted as due to a defective dopamine tone in the hypothalamus of Parkinsonian subjects on Madopar but not Sinemet therapy, a direct dopamine receptor agonist, lisuride was administered. Lisuride, however, elicited a blunted growth hormone response both in patients on Madopar and Sinemet therapy, without revealing a state of supersensitivity of dopamine receptors for growth hormone control in Parkinsonian subjects on Madopar therapy. No difference was present in the PRL-lowering effect of lisuride in the different experimental groups. These findings suggest that: (1) hypothalamic dopamine function is impaired in Parkinsonian subjects on Madopar therapy, preserved in unmedicated patients and enhanced in patients on Sinemet therapy; (2) the endocrine effects observed in Parkinsonian subjects on chronic Madopar therapy may be due to some penetration of benserazide across the blood brain barrier in the region of the hypothalamus; (3) since Madopar and Sinemet are in essence equally effective antiparkinsonian remedies, penetration of benserazide does not occur across the blood brain barrier surrounding the nigrostriatal system.

Adult↗
PubMed1987

The hydrodynamically balanced system: a novel principle of controlled drug release.

Madopar HBS (125 mg) is a controlled-release dosage form with 100 mg L-dopa and 25 mg benserazide. The 'hydrodynamically balanced system' (HBS) used for this novel dosage form of Madopar is a dosage form which, when in contact with gastric fluid and after dissolution of the gelatine shell of the capsule, forms a mucous body and a bulk density of less than 1 and releases the drug(s) at a desired rate whereas the dosage form remains in the stomach for a prolonged period of time. Drugs--in the present case L-dopa and benserazide--are released through the hydrated layer by diffusion principle. This system is valuable for drugs which are soluble at lower pH. By varying the composition of the excipients, desired release rates can be achieved. The in vitro dissolution rate of Madopar HBS formulation is as follows: L-dopa t75% = about 6 h and benserazide t75% = about 4 h. The floating behavior was tested in an in vitro test. These in vitro floating properties could be confirmed in man and were investigated in 10 healthy volunteers by means of gamma camera measurements using a poly-marker technique carried out in connection with a Valium CR study. It is expected that this novel drug delivery system proffers a valuable dosage form which delivers the drug at a specific rate allowing a better control of fluctuations in parkinsonian patients.

Administration, Oral↗
PubMedDate not supplied

Clinical, endocrine, roentgenographic, and immune characterization of hyperprolactinemic women.

Seventy-one hyperprolactinemic women were analyzed for medical history, gonadotropin and ovarian hormonal levels, and prolactin (PRL) responsiveness to benserazide. Sellar tomography was then performed on a yearly basis for 3 years in all women, computerized coronal and sagittal tomography in 54 of them. Under basal conditions, 30 women had roentgenographic evidence of pituitary adenoma; at the end of the follow-up period, such evidence was seen in 44. Amenorrhea, steady PRL levels, a low LH/FSH ratio, a longer duration of the disease, and low serum progesterone levels were more common in women with a final diagnosis of pituitary adenoma than in those with a persistently normal sella. The benserazide test for PRL release had yielded abnormal results since the beginning in all the 44 women with final roentgenographic evidence of pituitary adenoma, and in about half of the patients with persistently normal aspect of the sella; autoantibodies towards the pituitary gland, the thyroid gland, and gastric parietal cells were found in 3, 2, and 3 patients, respectively. No autoantibodies towards the adrenal gland or the islets of Langerhans were ever found in any cases. These data show that a fair proportion of hyperprolactinemic women have a (micro)adenoma, which becomes apparent over a relatively short period of time. Amenorrhea and steadily raised PRL levels are more common in these women. The benserazide test seems to be adequate for predicting which women will eventually develop a roentgenographically detectable adenoma. Autoimmunity does not seem to be involved in the pathogenesis of hyperprolactinemia and/or pituitary adenoma.

Adenoma↗
PubMed1996

A study on the effect and tolerance of lisuride on Parkinson's disease.

Seventeen idiopathic parkinsonian patients ranging between 47 and 75 years of age were included in this study to investigate the effect and tolerance of lisuride on PD. The duration of this simple clinical study, which had no control group was 12 weeks. There was 50% relief in disability scores and ADL in 13 patients in the first group in the combined therapy for 12 weeks with lisuride added to L-DOPA plus benserazide (p < 0.01). Optimal lisuride doses added to L-DOPA plus benserazide varied between 0.1 and 0.8 mg (mean 0.5 +/- 0.2 mg). With the addition of lisuride to treatment, the L-DOPA plus benserazide dose was reduced in 6 of 13 by 38%. Monotherapy with lisuride resulted in 56% to 57% improvement in disability scores and 47% in relief in ADL. Dry mouth, nausea, weakness, postural hypotension, and headache were the most frequently encountered side effects of lisuride. These adverse effects disappeared in 3 or 4 days, depending on a slight decrease and following increase in the dose of lisuride and/or the development of tolerance. Not only will such a combined therapy contribute to the reduction of the end-of-dose inadequacies, on-off phenomena, wearing off, peak-dose dyskinesias, and similar motor fluctuations, it may also play a prophylactic role in their prevention or delay.

Age of Onset↗
PubMed2004

Semi-chronic increase in striatal level of 3,4-dihydroxyphenylacetaldehyde does not result in alteration of nigrostriatal dopaminergic neurones.

This work was carried out to evaluate the potential in vivo toxicity of 3,4-dihydroxyphenylacetaldehyde (DOPAL), an aldehyde formed from dopamine by monoamine oxidase (MAO) that is oxidised mainly to 3,4-dihydroxyphenylacetic acid (DOPAC) by brain aldehyde dehydrogenases (ALDH). In this study, male Sprague-Dawley rats were treated with levodopa (L-dopa)-benserazide, which increases DOPAL production by MAO, and disulfiram, an irreversible inhibitor of ALDH, which reduces the formation of DOPAC from DOPAL. An acute systemic intraperitoneal (i.p.) injection of 100 mg/kg disulfiram and L-dopa-benserazide (100 mg/kg + 25 mg/kg, 24 hr later) significantly increased DOPAL striatal level. A 30-day treatment with disulfiram (100 mg/kg i.p., once every 2 days) and L-dopa-benserazide (100 mg/kg + 25 mg/kg, two times/day) did not affect either indexes used to assess integrity of the nigrostriatal dopaminergic neurones (i.e., the striatal content in dopamine and binding to the vesicular monoamine transporter on striatal membranes). These results do not evidence any deleterious effect of DOPAL and argue against toxicity of L-dopa therapy.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1983

Cardiovascular and biochemical effects of L-DOPA in the sea-gull, Larus argentatus.

We have investigated the effects of L-DOPA alone and in combination with three different inhibitors of L-aromatic aminoacid decarboxylase (DC), carbidopa, benserazid and alpha-monofluoromethyldopa (MFMD) on blood pressure (BP) and catecholamine content in conscious or anaesthetized sea-gulls, Larus argentatus. The results show that L-DOPA, given i.p., is taken up and decarboxylated to dopamine (DA) in brain and heart. Carbidopa inhibits the peripheral synthesis of DA from exogenous L-DOPA while central decarboxylation is enhanced when compared to the effects of L-DOPA alone. Benserazid and MFMD inhibit both central and peripheral formation of DA after L-DOPA injections. L-DOPA given alone leads to a slight increase in BP, while heart rate (HR) decreases somewhat. After peripheral inhibition of DC using carbidopa, L-DOPA elicits a reduction in BP both in conscious and anaesthetized birds. HR is significantly reduced in anaesthetized birds. Pretreatment with benserazid or MFMD abolishes the cardiovascular effects of L-DOPA. It is concluded that L-DOPA lowers the BP via activation of central mechanisms.

Animals↗
PubMed1987

Studies on the central action of L-threo-3,4-dihydroxyphenyl-serine (L-threo-DOPS) in FLA-63-treated mice.

In order to clarify the central action of L-threo-DOPS, the effect of benserazide on behavioral and biochemical changes by L-threo-DOPS in FLA-63-treated mice was studied. L-threo-DOPS in combination with nialamide markedly increased both the locomotor activity and the concentrations of the brain, heart and kidney norepinephrine (NE) in the FLA-63-treated mice. Benserazide at low doses did not alter either the rise of the brain NE level or the increase in locomotor activity, whereas it significantly inhibited the rise of the heart and kidney NE levels. Benserazide at a high dose significantly inhibited all of them. These results suggested that the increase in locomotor activity might be mediated via activation of the central noradrenergic neurons system by L-threo-DOPS.

Animals↗
PubMed1999

Acute interactions between L-DOPA and the neurotoxic effects of 1-methyl-4-phenylpyridinium or 6-hydroxydopamine in mice.

We have compared the effects of an i.p. pretreatment with L-DOPA (200 mg/kg) associated with benserazide (25 mg/kg) on neurotoxic effects of either 6-hydroxydopamine (6-OHDA) (50 microg, 10 microl per mouse) or 1-methyl-4-phenylpyridinium (MPP+) (17.5 microg, 10 microl per mouse). The striatal dopamine (DA) content, the vesicular monoamine transporter (VMAT2) density, as well as the hypothalamic norepinephrine (NE) content were measured 8 days after treatments. The L-DOPA-benserazide pretreatment worsened by 65% the 6-OHDA-induced depletion in striatal DA. On the contrary, it reduced by 42% the MPP+-induced depletion in striatal DA and by 54% the MPP+-induced decrease in VMAT2 density. It was noticed that the L-DOPA-benserazide pretreatment did not modify the marked decrease in hypothalamic NE content induced by 6-OHDA.

1-Methyl-4-phenylpyridinium↗
PubMed1991

Effects of levodopa and bromocriptine on blood pressure and plasma catecholamines in parkinsonians.

Blood pressure (BP), heart rate (HR), plasma noradrenaline (NA), and adrenaline (A) levels in the lying and standing position were compared in patients with Parkinson's disease (PD) and control subjects. Three groups of PD patients (stage 2 and 3) were investigated: six patients deprived of antiparkinsonian drugs from 48 h, seven levodopa + benserazide-treated patients, and seven bromocriptine-treated patients. BP, HR, NA, and A were similar at rest and in the standing position in controls and in PD patients deprived of antiparkinsonian drugs from 48 h. Chronic treatment with levodopa (+ benserazide) failed to modify BP, HR, NA, and A. Bromocriptine decreased BP, HR, and NA (but not A) at rest. In PD patients treated with levodopa (+ benserazide) or bromocriptine alone, the rise in NA (but not A) elicited by standing up was reduced. These results indicate that (a) stages 2 to 3 of Parkinson's disease are not accompanied by major changes in autonomic cardiovascular function and (b) dopaminergic drugs blunted the sympathetic response to standing up.

Aged↗
PubMed1996

The depletion of brain serotonin levels by para-chlorophenylalanine administration significantly alters the activity of midbrain dopamine cells in rats: an extracellular single cell recording study.

In this study, we examined the effect of 5-HT depletion produced by the acute administration of para-chlorophenylalanine (PCPA) on the number of spontaneously active dopamine (DA) cells in the ventral tegmental area (VTA or A10) and substantia nigra pars compacta (SNC or A9) in the rat. We also determined the effect of PCPA administration on the spike discharge pattern of midbrain DA cells. This was accomplished using standard extracellular single cell recording techniques. The administration of PCPA (400 mg/kg, i.p., 24 h before the experiment) produced a significant decrease in the number of spontaneously active DA cells in both the A9 (52%) and A10 (63%) areas compared to controls. The burst firing analysis indicated that there was a significant increase in the mean interspike interval of A9 and A10 DA neurons in PCPA treated animals compared to controls. Furthermore, a decrease in the percentage of A10 DA neurons exhibiting a burst firing pattern and the number of bursts was observed in the PCPA treated animals compared to controls. The intravenous (i.v.) administration of 5-hydroxytryptophan (40 mg/kg) and the peripheral aromatic acid decarboxylase inhibitor benserazide (10 mg/kg) which restores 5-HT content, reversed the decrease in the number of spontaneously active A9 and A10 DA neurons, as well as the decrease in the percentage of A10 DA neurons exhibiting a bursting pattern. In contrast, the i.v. administration of benserazide (10 mg/kg) and L-DOPA (40 mg/kg) did not reverse the decrease in the number of spontaneously active midbrain DA neurons produced by PCPA treatment. The pretreatment of animals with PCPA did not alter the sensitivity of spontaneously active A9 or A10 DA cells to the intravenous administration of (+)-apomorphine (1-32 micrograms/kg) compared to controls. Overall, our results indicate that the depletion of brain 5-HT by PCPA produces a decrease in the activity of midbrain DA cells, suggesting that endogenous 5-HT is required to maintain DA tone.

5-Hydroxytryptophan↗
PubMed1989

Induction of aromatic-L-amino acid decarboxylase by decarboxylase inhibitors in idiopathic parkinsonism.

We evaluated the effect of administration of L-dopa, alone or in combination with a peripheral decarboxylase inhibitor, on plasma levels of aromatic-L-amino acid decarboxylase (ALAAD). After single-dose administration of L-dopa plus benserazide (Madopar) in healthy subjects and in chronically treated patients with parkinsonism, plasma ALAAD followed for 2 to 3 hours fell, but returned to predosing levels within 90 minutes. Four groups of patients with idiopathic parkinsonism were studied during chronic treatment: Group I, no L-dopa treatment (n = 31); Group II, L-dopa alone (n = 15); Group III, L-dopa plus benserazide (n = 28); and Group IV, L-dopa plus carbidopa (Sinemet, n = 30). Plasma ALAAD 2 hours after dosing was normal in Groups I and II. ALAAD was increased threefold in Groups III and IV, suggesting induction of ALAAD by the coadministration of a peripheral decarboxylase inhibitor. In a study of 3 patients in whom L-dopa/benserazide was started, plasma ALAAD rose gradually over 3 to 4 weeks. Further detailed pharmacokinetic studies of L-dopa, dopamine, and ALAAD in plasma and cerebrospinal fluid are required to determine if the apparent ALAAD induction by a peripheral decarboxylase inhibitor may be related to the loss of clinical efficacy of combination therapy in some patients and how it is related to end-of-dose deterioration and on-off phenomena.

Aged↗
PubMed1986

Conditioned taste aversion and conditioned drinking: two independent and opposing effects of 5-hydroxytryptophan?

Four experiments were carried out to examine the effects of 5-HTP in a conditioned taste aversion (CTA) paradigm. Using two-choice tests to measure the CTA, administration of 5-HTP following consumption of a novel flavour caused aversions to saline and saccharin solutions. In single-choice tests 5-HTP reduced consumption of saccharin, sugar cubes and beef-flavoured stock cubes, but only reduced saline consumption if animals had been pretreated with the 5-HTP decarboxylase inhibitor benserazide or the 5-HT receptor antagonist xylamidine, both of which act peripherally. Benserazide did not attenuate the CTA in any experiment. The results are interpreted in terms of two competing behavioural effects of 5-HTP: a centrally-mediated CTA and a peripherally-mediated conditioned drinking response.

5-Hydroxytryptophan↗
PubMed1989

Treatment of idiopathic parkinsonism with L-dopa in the absence and presence of decarboxylase inhibitors: effects on plasma levels of L-dopa, dopa decarboxylase, catecholamines and 3-O-methyl-dopa.

The effect of levodopa (L-dopa), alone or in combination with a peripheral decarboxylase inhibitor (PDI), on plasma levels of aromatic-L-amino acid decarboxylase (ALAAD, = dopa decarboxylase), L-dopa, 3-O-methyl-dopa (3-OMD), dopamine (DA), noradrenaline, adrenaline and dopamine beta-hydroxylase has been studied. In healthy subjects and in patients with parkinsonism plasma ALAAD level fell after administration of L-dopa + benserazide, but returned to previous levels within 90 min. In a cross-sectional study blood was obtained, 2 h after dosing, from 104 patients with idiopathic parkinsonism, divided into four groups: no L-dopa treatment (group 1), L-dopa alone (group 2), L-dopa + benserazide (Madopar) (group 3) and L-dopa + carbidopa (Sinemet) (group 4). Plasma ALAAD, which was normal in groups 1 and 2, was increased 3-fold in groups 3 and 4, indicating that there was induction of ALAAD by the co-administration of PDI. Despite this induction of ALAAD, in groups 3 and 4, with half the daily L-dopa dose compared with group 2, plasma L-dopa and 3-OMD levels were 5 times higher, while plasma DA levels were not different. The DA/L-dopa ratio was decreased 5-fold in group 2 and 16-fold in groups 3 and 4 as compared with group 1. Neither 3-OMD levels nor 3-OMD/L-dopa ratios correlated with the occurrence of on-off fluctuations. In a longitudinal study of three patients started on Madopar treatment the induction of plasma ALAAD was found to occur gradually over 3-4 weeks. Further detailed pharmacokinetic studies in plasma and cerebrospinal fluid are required in order to elucidate whether the ALAAD induction by PDI may be related to the loss of clinical efficacy of combination therapy in some patients and how it is related to end-of-dose deterioration and on-off phenomena.

Administration, Oral↗
PubMed1983

Intestinal absorption of levodopa in man.

In four healthy subjects the intestinal absorption of levodopa (l-dopa) was investigated by measuring the plasma concentration of the amino acid following the administration of l-dopa at three different sites in the small intestine. In order to minimize presystemic clearance of l-dopa, the subjects were pretreated with the peripheral decarboxylase inhibitor benserazide 3 X 50 mg every 8 h on the previous day and 1 X 50 mg 2 h prior to administration of the l-dopa. L-dopa 100 mg dissolved in 0.05 N HCl and 50 mg benserazide dissolved in 0.05 N HCl were coadministered. Under these conditions no difference in tmax, cmax or AUC of l-dopa was observed between administration of the drug into the proximal or the distal part of duodenum, or into the upper part of jejunum. The results indicate that in healthy subjects, during inhibition of peripheral decarboxylase, the rate and extent of l-dopa absorption does not differ at any site in the upper small intestine.

Adult↗
PubMed1995

Effects of tolcapone, a novel catechol-O-methyltransferase inhibitor, on striatal metabolism of L-dopa and dopamine in rats.

In vivo brain microdialysis was used to assess the effects of tolcapone, a novel central and peripheral inhibitor of catechol-O-methyltransferase on striatal 3,4-dihydroxyphenyl-L-alanine (L-dopa) and dopamine metabolism. The oral administration of 30 mg/kg of tolcapone failed to change dopamine output but elicited a marked and long-lasting decrease of the extracellular levels of homovanillic acid (HVA) and 3-methoxytyramine with a concomitant increase of 3,4-dihydroxyphenylacetic acid (DOPAC). The administration of L-dopa (20 and 60 mg/kg p.o.) + benserazide (15 mg/kg p.o.) resulted in dose-dependent increase of dialysate levels of L-dopa and 3-O-methyl-DOPA. Tolcapone (30 mg/kg p.o.), given as adjunct to both doses of L-dopa, markedly enhanced the elevation or extracellular L-dopa, while it completely prevented the formation of 3-O-methyl-DOPA. In another experiment, the administration of L-dopa + benserazide (30 + 15 mg/kg p.o.) resulted in increased extracellular levels of dopamine, DOPAC, HVA and 3-methoxytyramine. The co-administration of tolcapone (30 mg/kg p.o.) further increased dopamine and DOPAC levels, whereas HVA and 3-methoxytyramine effluxes were reduced. These findings support the notion that tolcapone has the ability to enhance striatal dopamine neurotransmission by increasing L-dopa bioavailability through peripheral and central inhibition of L-dopa O-methylation, as well as by blocking the central conversion of dopamine into 3-methoxytyramine.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1995

Antagonism by the 5-HT2A/C receptor agonist DOI of raclopride-induced catalepsy in the rat.

It has been shown that the administration of 5-hydroxytryptamine (5-HT)1A receptor agonists will antagonize the catalepsy induced by dopamine D1 or D2 receptor blocking agents. In the present study, administration of the 5-HT2A/C receptor agonist, 1-(2,5-dimethoxy-4-iodo)-2-aminopropane (DOI) (1 mg kg-1 s.c.), counteracted the catalepsy produced by the dopamine D2 receptor antagonist, raclopride (16 mg kg-1 s.c.), but not by the dopamine D1 receptor antagonist (R)-(+)-8-chloro-2,3,4,5-tetra-hydro-3-methyl-5-phenyl-1H-3-benzazepine (SCH 23390) (0.2 mg kg-1 s.c.). The effects of DOI on raclopride-induced catalepsy were fully antagonized by pretreatment with the 5-HT2A/C receptor antagonist, ritanserin (2 mg kg-1 s.c.). The 5-HT precursor, 5-hydroxytryptophan (5-HTP) (6.25-25.0 mg kg-1 i.p.), in combination with the peripheral 5-HTP decarboxylase inhibitor, benserazide (25 mg kg-1 i.p.), and the selective serotonin reuptake inhibitor, zimeldine (10 mg kg-1 s.c.), enhanced the catalepsy produced by a low dose of raclopride (4 mg kg-1 s.c.). It is concluded that stimulation of (postsynaptic) 5-HT2 receptors results in antagonism of the catalepsy induced by treatment with a dopamine D2, but not a D1, receptor antagonist. The fact that 5-HTP, in the presence of benserazide and zimeldine, enhanced raclopride-induced catalepsy suggests the possibility of postsynaptic 5-HT receptors acting in opposition to the 5-HT1 and 5-HT2 receptors, as regards extrapyramidal motor functions in the rat.

5-Hydroxytryptophan↗