An investigation into the effects and possible mechanisms of action of cimetidine and ranitidine on the sexual behaviour of male rats.
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Date
1985
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Abstract
The development of a new class of antihistamines, the
H2-receptor antagonists, introduced a new era in the
treatment of peptic ulcer diseases. Cimetidine, the first
clinically effective H2-blocker, was introduced in 1976.
Recently ranitidine, a second member approved for clinical
use, has been found to be as effective as cimetidine in
the management of peptic ulcer diseases. Soon after the
introduction of cimetidine several reports of loss of
libido, impotence and gynaecomastia were described in male
patients who were on normal or high therapeutic doses of
cimetidine. A few unsubstantiated reports of loss of
libido and gynaecomastia attributed to ranitidine therapy
have also appeared in literature.
This study was undertaken to examine in detail the effects
of acute and subchronic treatment with cimetidine and
ranitidine on mating behaviour in sexually active male
rats. Motor activity counts were recorded immediately
before sexual behaviour observations. The animals were
tested on every third day and observations were terminated
after the first intromission of the next series of
copulations. In the single dose study, mating behaviour
tests were commenced 2 hours after treatment; mating tests
during the subchronic dose studies were done 4 to 7 hours
after the 6hOO dose. The following measures were used in
the analysis of data: mount latency, intromission latency,
mount frequency, intromission frequency, ejaculation
latency, and the postejaculatory intromission latency. At
the termination of the subchronic dose studies blood
samples were collected by cardiac puncture and the animals
were subsequently autopsied. Cauda epididymal sperm counts
and motility were determined, testes and accessory sex
organs were weighed, and one testis was processed for
histological examination.
Cimetidine in the low dose, 128.6 mg/kg, significantly
shortened the ejaculatory latency and to a lesser extent
the postejaculatory intromission latency. At the higher
dose, 257.1 mg/kg, cimetidine markedly prolonged the
postejaculatory intromission latency and to a lesser
extent increased the ejaculation latency. The inhibitory
effect of cimetidine on copulatory behaviour at the higher
dose level was accompanied by significant depression in
motor activity.
At the conclusion of the subchronic dose studies marked
reductions in serum testosterone levels and decreased
testes and accessory organ weights were observed in the
cimetidine group. No significant changes in sperm counts
were observed, although the sperm counts in the cimetidine
group were lower than the control values. Histological
examination of testes showed apparently normal
spermatogenesis in all three treatment groups.
However, in spite of the reduced testosterone levels and
decreased testes and accessory sex organ weights in the
cimetidine group, no impairment in mating behaviour was
observed.
In both the acute and the subchronic dose studies, similar
to placebo, treatment with ranitidine showed no effect on
mating behaviour.
On final analysis of the results it is concluded that
cimetidine, and not ranitidine, disrupts sexual behaviour
in male rats. Furthermore, it is concluded that the effect
of cimetidine on sexual behaviour is not related to
H2-receptor blockade as equipotent doses of ranitidine did
not produce similar effects. The mechanism of
cimetidine-induced impairment of sexual performance in the
male rat may possibly be attributed to some non-specific,
direct or indirect action of cimetidine on some
neurotransmitter system responsible for the control of
sexual behaviour. It is further suggested that the effect
may possibly be mediated by a blockade of central dopamine
receptors. However, it must be stressed that further
experimentation is necessary to elucidate the mechanism of
action of cimetidine on sexual behaviour.
Description
Thesis (M.Sc.)-University of Durban-Westville, 1985.
Keywords
Cimetidine., Ranitidine., Antihistamines., Rats as laboratory animals., Theses--Pharmacy and pharmacology.